Comparative effectiveness of dapagliflozin vs . empagliflozin on major adverse cardiovascular events in patients with heart failure with reduced ejection fraction: A real‐world prospective cohort study

BACKGROUND: Dapagliflozin and empagliflozin are sodium-glucose cotransporter-2 inhibitors (SGLT2i) with equivalent Class IA guideline recommendations in heart failure with reduced ejection fraction (HFrEF). OBJECTIVES: To compare the incidence of major adverse cardiovascular events (MACE) between dapagliflozin and empagliflozin in HFrEF patients treated in routine clinical practice. METHODS: This prospective real-world cohort study enrolled 1231 consecutive HFrEF patients (left ventricular ejection fraction ≤40%) at Can Tho Central General Hospital, Vietnam (March 2023 to March 2026). Patients received dapagliflozin (n = 622) or empagliflozin (n = 609) as part of optimized guideline-directed medical therapy and the primary outcome was MACE. RESULTS: MACE occurred in 64 patients (10.3%) receiving dapagliflozin and 111 patients (18.2%) receiving empagliflozin. Following propensity score matching and multivariable adjustment, dapagliflozin was associated with significantly lower odds of MACE (adjusted odds ratio OR 0.46; 95% confidence interval CI 0.30, 0.67; p < 0.001). Hospitalization for heart failure was significantly lower with dapagliflozin (8.7% vs. 14.9%; adjusted OR 0.52; 95% CI 0.33, 0.80; p = 0.003). Corrected all-cause mortality was 13/622 (2.1%) with dapagliflozin and 25/609 (4.1%) with empagliflozin (p = 0.048). Multivariable logistic regression identified four independent predictors of MACE: New York Heart Association functional class III-IV (adjusted OR 15.54; 95% CI 9.09, 28.99; p < 0.001), sedentary lifestyle (adjusted OR 2.11; 95% CI 1.42, 3.37; p < 0.001), premature cardiovascular disease history (adjusted OR 2.30; 95% CI 1.29, 4.43; p = 0.007) and dapagliflozin as an independent protective factor (adjusted OR 0.47; 95% CI 0.31, 0.68; p < 0.001). CONCLUSIONS: In this real-world prospective Vietnamese HFrEF cohort followed over 36 months, dapagliflozin was associated with significantly lower odds of MACE and HF hospitalization compared with empagliflozin, with robust adjustment for confounding.