Timing matters: clinical outcomes of early sodium-glucose cotransporter-2 inhibitor initiation in acute heart failure
B L Resende, A M Pinto, E Mata, J Portugues, G Costa, S Ribeiro, J Gameiro, A Lourenco, L GoncalvesAbstract
Background
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.
Methods
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.
Results
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.
Conclusion
Initiation of SGLT2i during AHF hospitalization significantly improves survival without increasing adverse safety events, supporting their use as an early adjunct to guideline-directed therapy. The absence of a clear effect on rehospitalization highlights the need for further large-scale and patient-level analyses.For image description, please refer to the figure legend and surrounding text.