Mortality and Heart Failure Hospitalization in Patients With HFpEF on Mineralocorticoid Receptor Antagonists: A Systematic Review and Meta-Analysis.

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.