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Timing matters: clinical outcomes of early sodium-glucose cotransporter-2 inhibitor initiation in acute heart failure

B. Resende, A. M. Pinto, E. Mata, J. Português, G. Costa, S. Ribeiro, J. Gameiro, A. Lourenço et al.

European Journal of Heart Failure, 2026

3,596 participants

Abstract

Acute heart failure (AHF) remains associated with high short-term mortality and rehospitalization despite advances in therapy. Sodium–glucose cotransporter2 inhibitors (SGLT2i) provide robust cardiovascular benefits in heart failure, but their efficacy and safety when initiated during AHF hospitalization are less well established.

Following a systematic search of five 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. Primary outcomes were all-cause mortality and heart failure hospitalization (HFH). Secondary outcomes included all-cause mortality at 1-month, cardiovascular death, serious adverse events leading to drug discontinuation, acute kidney injury (AKI), hypotension, hypoglycemia, and diabetic ketoacidosis. Data were pooled using inverse variance random-effects models.

Eight RCTs including 3596 patients (1817 SGLT2i; 1779 control) were analyzed. SGLT2i initiation in AHF significantly reduced all-cause mortality (RR 0.63, 95% CI 0.46–0.85; P = 0.003; I² = 0%). No significant reduction was observed for HFH (RR 0.86, 95% CI 0.69–1.07; P = 0.78; I² = 0%). All-cause mortality at 1 month and cardiovascular death, did not differ significantly between groups. Pooled analyses showed no excess risk of hypotension, hypoglycemia, AKI or ketoacidosis.

Initiation of SGLT2i during…

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