Efficacy and Safety of Early Initiation of Sodium-Glucose Cotransporter 2 Inhibitors in Acute Heart Failure: A Systematic Review and Meta-Analysis

BACKGROUND AND OBJECTIVES: Acute heart failure (AHF) remains associated with high short-term mortality and rehospitalization despite advances in therapy. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) provide robust cardiovascular benefits in heart failure, but their efficacy and safety when initiated during AHF hospitalization are less established. METHODS: Following a systematic search of 4 databases, a systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the efficacy and safety of the initiation of dapagliflozin or empagliflozin during hospitalization for AHF, in addition to standard therapy. The primary outcome was all-cause mortality. Secondary outcomes included heart failure hospitalization (HFH), all-cause mortality at 1 month, cardiovascular death, serious adverse events leading to drug discontinuation, acute kidney injury (AKI), urinary tract infection (UTI), symptomatic hypotension, hypoglycemia, and diabetic ketoacidosis. Data were pooled using random-effects models, with sensitivity and meta-regression analyses. RESULTS: Eight RCTs including 3,596 patients (1,817 SGLT2i; 1,779 control) were analyzed. SGLT2i initiation in AHF significantly reduced all-cause mortality (risk ratio [RR], 0.63; confidence interval [CI], 0.46-0.85; I²=0%) and all-cause mortality at 1 month (RR, 0.75; CI, 0.57-0.98; I²=0%). HFH and cardiovascular death did not differ significantly between groups. Pooled analyses showed no excess risk of serious adverse events leading to drug discontinuation, AKI, UTI, symptomatic hypotension, hypoglycemia or ketoacidosis. CONCLUSIONS: Initiation of SGLT2i during AHF hospitalization significantly improves survival without increasing adverse safety events, supporting their use as an early guideline-directed therapy. The absence of a clear effect on HFH highlights the need for further large-scale and patient-level analyses. TRIAL REGISTRATION: PROSPERO Identifier: CRD420251140155.