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

Background Observational studies and small randomized controlled trials have suggested the benefits of early introduction of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in acute heart failure (AHF). However, current evidence on their efficacy and safety in this clinical setting remains limited.Methods We performed a systematic review and meta-analysis to assess efficacy/safety of early use of SGLT2is in AHF. PUBMED/EMBASE/Cochrane were searched from inception to May 31, 2024, for randomized controlled trials evaluating outcomes of SGLT2i early initiation in patients with AHF. Efficacy outcomes were all-cause death and heart failure rehospitalizations. Safety outcomes included acute kidney injury, ketoacidosis, urinary tract infections, hypotension, and hypoglycemia. Early initiation was defined as performed before or shortly after discharge (within 3 days). A sensitivity analysis was conducted, including only patients with initiation before discharge.Results Seven randomized controlled trials that enrolled 2320 patients were included. Early use of SGLT2is was associated with a significant reduction in all-cause death (odds ratio, 0.71 [95% CI, 0.55-0.92; 95% PI, 0.55-0.98]) and HF rehospitalizations (odds ratio, 0.73 [95% CI, 0.57-0.94; 95% PI, 0.58-0.93]), even after adjusting for follow-up duration. SGLT2i initiation before discharge yielded consistent results for efficacy outcomes. Safety outcomes could not be usefully determined because of a low events rate resulting in wide CIs. The impact of diabetic status remains basically unknown due to the small number of available randomized controlled trials investigating this population.Conclusions Early introduction of SGLT2is in AHF improves all-cause death and rehospitalization rates, can be performed before discharge, and should be offered to most patients with AHF.