EvidenceAlerts

Knezevic-Maragh M, Gilani F, Nandakumar NA, et al. Mortality and Heart Failure Hospitalization in Patients with HFpEF on Mineralocorticoid Receptor Antagonists: A Systematic Review and Meta-Analysis. Am J Cardiol. 2026 May 12:S0002-9149(26)00341-3. doi: 10.1016/j.amjcard.2026.05.009. (Systematic review)
Abstract

Heart failure with preserved ejection fraction (HFpEF) is highly prevalent and associated with substantial morbidity and mortality. The clinical benefit of mineralocorticoid receptor antagonist (MRA) therapy in this population remains uncertain. A meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, searching PubMed, Embase, and Scopus from inception through the most recent available data to identify randomized controlled trials and observational cohort studies comparing MRAs with placebo or no MRA therapy in adults with HFpEF. Primary outcomes were all-cause mortality, cardiovascular mortality and HF hospitalization, while secondary outcomes included hyperkalemia. Random-effects models were used to pool risk ratios (RRs) or hazard ratios with 95% confidence intervals (CLs). Twenty-one reports representing 11 unique studies comprising 50,983 patients met the inclusion criteria; 8,976 received MRA therapy, and 28,999 served as controls. MRA use was not associated with a statistically significant reduction in all-cause mortality (RR 0.91, 95% CI 0.81 to 1.02) or cardiovascular mortality (RR 0.84, 95% CI 0.66-1.05; p = 0.13). MRA therapy, however, was associated with a significant reduction in HF hospitalization (RR 0.81, 95% CI 0.73 to 0.90; p <0.0001). MRA use was also associated with an increased risk of hyperkalemia (RR 2.04, 95% CI 1.55 to 2.68; p <0.00001). In conclusion, MRA therapy in HFpEF reduces HF hospitalization without a significant mortality benefit and is associated with increased hyperkalemia risk.

Ratings
Discipline Area Score
Family Medicine (FM)/General Practice (GP) 6 / 7
General Internal Medicine-Primary Care(US) 6 / 7
Internal Medicine 6 / 7
Cardiology 5 / 7
Comments from MORE raters

Family Medicine (FM)/General Practice (GP) rater

This is important input in the discussion on the treatment of patients with HFpEF, helping us make informed decisions. MRAs can cause some benefits as well as remarkable harms in this group of HF patients. Although reductions in hospital admissions are important, the lack of significant influence on mortality makes MRAs questionable in HFpEF.

Internal Medicine rater

Mineralocorticoid receptor antagonists do not show any mortality benefit, but they reduce heart failure-related hospitalizations. That is a significant step towards better quality of life for patients with heart failure with preserved ejection fraction.
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