Heart Failure With Reduced Ejection Fraction and SGLT2 Inhibitors- Clinical Outcomes, Adverse Events, and Comorbidities Over Three Years: A Retrospective Cohort Study

Abstract

Background: Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors are now a cornerstone therapy for Heart Failure with reduced Ejection Fraction (HFrEF), with demonstrated benefits in survival and hospitalization reduction. However, most evidence is limited to 12–18 months of follow-up. Methods: We conducted a retrospective cohort study using electronic health record data from 11,113 patients with HFrEF (LVEF ≤ 40%) between 2014 and 2024. Patients were stratified based on SGLT2 inhibitor use and matched 1:1 using propensity scores on demographics, comorbidities, and guideline-directed medical therapy. Primary outcomes included all-cause mortality and hospitalizations for Heart Failure (HF), Acute Coronary Syndrome (ACS), Acute Kidney Injury (AKI), and Urinary Tract Infection (UTI). Cox proportional hazards and Fine-Gray competing risk models were used for analysis. Results: Over three years, SGLT2 inhibitor use was associated with a 35% reduction in all-cause mortality (Hazard Ratio (HR) 0.65, 95% CI 0.52–0.80; p < 0.001). SGLT2 inhibitors were also linked to lower risks of heart failure hospitalization (SHR 0.61, 95% CI 0.47–0.80; p<0.001), ACS admissions (SHR 0.22, 95% CI 0.13–0.37; p<0.001), AKI admissions (SHR 0.36, 95% CI 0.25–0.54; p<0.001), and UTI admissions (SHR 0.13, 95% CI 0.03–0.58; p=0.007). Conclusions: Sodium-glucose cotransporter 2 inhibitor use in heart failure with reduced ejection fraction was associated with significantly improved long-term survival and a substantial reduction in heart failure and acute coronary syndrome hospitalizations, without increased risk of AKI or UTI.