SGLT2 Inhibitors in Heart Failure with Preserved Ejection Fraction (HFpEF)

Abstract

Introduction: Heart failure with preserved ejection fraction (HFpEF) lacks effective therapies. SGLT2 inhibitors (empagliflozin, dapagliflozin) reduce hospitalization in HFrEF; their role in HFpEF is now established. Methods: Systematic review and meta-analysis of 3 RCTs (n=7,896) (EMPEROR-Preserved, DELIVER, PRESERVED-HF). Inclusion: LVEF ≥40%, NYHA II–IV, NT-proBNP elevated. Primary composite outcome: cardiovascular death or HF hospitalization. Secondary: total HF hospitalizations, Kansas City Cardiomyopathy Questionnaire (KCCQ). Results: SGLT2i reduced primary outcome by 17% (HR 0.83, 95% CI 0.76–0.90, p<0.001). Benefit was consistent across EF subgroups (40–49%, 50–59%, ≥60%). Total HF hospitalizations reduced by 23% (RR 0.77). KCCQ improved by 3.4 points (p=0.001). Genital infections were increased (8% vs 2%, NNH=17). No increase in diabetic ketoacidosis or amputation. Discussion: SGLT2 inhibitors are the first drug class to show definitive benefit in HFpEF, likely via hemodynamic and metabolic effects rather than diuresis alone. Conclusion: Empagliflozin or dapagliflozin reduce HF hospitalization and improve quality of life in HFpEF.