JAMA Netw Open. 2025 Dec 1;8(12):e2546865. doi: 10.1001/jamanetworkopen.2025.46865.
ABSTRACT
IMPORTANCE: Sodium-glucose cotransporter-2 inhibitors have emerged as important therapeutic options for heart failure (HF). However, their comparative clinical effectiveness remains uncertain.
OBJECTIVE: To compare the outcomes associated with dapagliflozin and empagliflozin use in patients diagnosed with HF.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study used a clinical data warehouse platform shared by 8 medical centers affiliated with The Catholic University of Korea to screen all patients who were diagnosed with HF between January 2021 and November 2023 at these 8 medical centers. Patients were taking either dapagliflozin or empagliflozin and underwent transthoracic echocardiography. One-to-one propensity score matching was performed to ensure comparable baseline characteristics between groups. The propensity score-matched cohort was stratified by left ventricular ejection fraction (LVEF) into subgroups: HF with reduced ejection fraction group had an LVEF of 40% or lower, HF with mildly reduced ejection fraction group had an LVEF of 41% to 49%, and HF with preserved ejection fraction group had an LVEF of 50% or higher. Statistical analyses were performed from December 2023 to July 2025.
EXPOSURE: All patients received either dapagliflozin or empagliflozin.
MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of cardiovascular death or hospitalization for heart failure. Secondary outcomes included the individual primary outcome components, all-cause death, and cardiovascular hospitalization.
RESULTS: After propensity score matching, the balanced cohort included 4930 patients (2465 each in the dapagliflozin and empagliflozin group; mean [SD] age, 68.8 [13.4] years; 2944 males [59.7%]). The median (IQR) follow-up duration was 16.0 (8.0-27.0) months. In the propensity score-matched cohort, dapagliflozin and empagliflozin showed no significant difference in the primary outcome: a composite of cardiovascular death or HF hospitalization occurred in 9.8% of patients (241 of 2465) taking dapagliflozin vs 9.3% of patients (229 of 2465) taking empagliflozin (adjusted hazard ratio [AHR], 0.99; 95% CI, 0.83-1.19; P = .95). The results did not change after stratifying the cohort by LVEF 40% or lower (14.9% [126 of 844] vs 15.4% [132 of 855]; AHR, 1.06 [95% CI, 0.83-1.35; P = .64]), LVEF 41% to 49% (5.0% [17 of 343] vs 6.3% [22 of 350]; AHR, 1.28 [95% CI, 0.68-2.42; P = .45]), and LVEF 50% or higher (7.7% [98 of 1278] vs 6.0% [75 of 1260]; AHR, 0.80 [95% CI, 0.60-1.09; P = .32]), without between-group heterogeneity (P for interaction = .32). For the secondary outcomes, there were also no significant differences between the dapagliflozin and empagliflozin groups.
CONCLUSIONS AND RELEVANCE: In this cohort study of patients with HF, dapagliflozin and empagliflozin had similar clinical outcomes in HF management. Further research and clinical trials are necessary to validate these findings and inform clinical decision-making.
PMID:41343213 | DOI:10.1001/jamanetworkopen.2025.46865
