Early Initiation of Dapagliflozin in Acute Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Background/Objectives: Dapagliflozin is a foundational chronic heart failure therapy, but whether it retains benefit when initiated early during hospitalization for acute heart failure (AHF) remains uncertain. Methods: We searched MEDLINE, Embase, Scopus, and CENTRAL from inception to 26 January 2026 for randomized trials comparing early initiation of dapagliflozin 10 mg once daily with standard therapy in adults hospitalized for AHF (PROSPERO CRD420261364466). Two reviewers independently performed screening, extraction, and risk-of-bias assessment. Outcomes were pooled under random-effects models with Knapp–Hartung adjustment. Results: Ten trials enrolling 3507 participants (1769 in the dapagliflozin group and 1738 in the control group) were eligible. Dapagliflozin significantly reduced all-cause mortality (RR 0.67, 95% CI 0.52–0.86) and urinary tract infections (RR 0.52, 95% CI 0.35–0.76), while no significant differences were observed in cardiovascular death, MACEs, heart failure hospitalization, all-cause readmission, length of hospital stay, or body weight. Dapagliflozin was not associated with a significant increase in acute kidney injury, hypotension, or hypoglycemia, supporting a favorable safety profile. Conclusions: In adults hospitalized with acute heart failure (AHF), dapagliflozin significantly reduced all-cause mortality but not heart failure hospitalization during follow-up. Larger, adequately powered trials in patients with AHF, with prespecified analyses according to the timing of dapagliflozin initiation, are warranted.