Impact of Early SGLT2 Inhibitor Initiation on Mortality and Rehospitalization in Patients with Acute Decompensated Heart Failure

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated substantial cardiovascular benefits in chronic heart failure. However, the optimal timing of initiation during acute decompensated heart failure (ADHF) hospitalization and its impact on short-term and intermediate-term clinical outcomes remain insufficiently characterized. This study aimed to evaluate the effect of early in-hospital SGLT2 inhibitor initiation on all-cause mortality and heart failure rehospitalization in patients admitted with ADHF. Methods: A retrospective cohort study was conducted across two tertiary cardiac centers. A total of 742 patients hospitalized with ADHF were included: 318 who received SGLT2 inhibitors within 48 hours of admission (early initiation group) and 424 who received standard heart failure therapy without SGLT2 inhibitors during hospitalization (standard care group). The primary composite endpoint was all-cause mortality or first heart failure rehospitalization at 180 days. Secondary endpoints included individual components of the composite, in-hospital worsening heart failure events, change in N-terminal pro-B-type natriuretic peptide (NT-proBNP), length of hospital stay, and renal safety outcomes. Results: The primary composite endpoint occurred in 22.3% of the early initiation group versus 33.5% of the standard care group (hazard ratio [HR] 0.61, 95% CI 0.47–0.79, p < 0.001). All-cause mortality at 180 days was 8.2% versus 13.4% (HR 0.58, 95% CI 0.38–0.89, p = 0.012). Heart failure rehospitalization occurred in 16.4% versus 24.3% (HR 0.63, 95% CI 0.47–0.85, p = 0.002). The early initiation group demonstrated significantly greater NT-proBNP reduction at discharge (−48.2 ± 22.6% vs. −34.7 ± 24.1%, p < 0.001) and shorter median length of stay (6.3 ± 2.8 vs. 7.9 ± 3.4 days, p < 0.001). No significant differences in acute kidney injury, diabetic ketoacidosis, or urinary tract infections were observed between groups. Conclusion: Early in-hospital initiation of SGLT2 inhibitors within 48 hours of admission for ADHF was associated with significantly reduced all-cause mortality, lower heart failure rehospitalization rates, and greater neurohormonal decongestion without increased adverse events. These findings support the paradigm of prompt SGLT2 inhibitor initiation during acute heart failure hospitalization.