Evaluating the Clinical Outcomes of Empagliflozin in Heart Failure Patients With Preserved Ejection Fraction: A Systematic Review.

Heart failure with preserved ejection fraction (HFpEF) represents a significant clinical challenge due to its complex pathophysiology and limited therapeutic options. This systematic review evaluates the efficacy and safety of empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, in patients with HFpEF. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we analyzed 11 studies, predominantly from the EMPEROR-Preserved trial and its sub-analyses, investigating empagliflozin in HFpEF patients. Our findings consistently demonstrate that empagliflozin significantly reduces heart failure hospitalizations (HR 0.71, 95% CI 0.60-0.83) across diverse patient populations. This benefit was observed regardless of sex, age, diabetes status, blood pressure, and frailty levels, although effects were attenuated in patients with higher ejection fractions and in severely frail individuals. Notably, empagliflozin did not significantly reduce cardiovascular mortality, although a non-significant trend toward benefit was observed in certain subgroups. Additional benefits included slowed decline in renal function and improved quality of life measures. The safety profile was favorable across all studies, with good tolerability even in elderly and frail populations. These findings position empagliflozin as a valuable addition to the limited therapeutic armamentarium for HFpEF, particularly for reducing hospitalizations and improving symptoms, though its impact on mortality appears limited. Future research should focus on identifying specific HFpEF phenotypes that derive maximal benefit from empagliflozin and evaluating its long-term efficacy, optimal combination strategies, and real-world effectiveness across diverse populations.