Efficacy and Safety of SGLT2 Inhibitors for Preventing Heart Failure in Post-Myocardial Infarction Patients Without Established Heart Failure: A Systematic Review and Meta-Analysis

Background Heart failure remains a major complication following myocardial infarction, affecting up to 30% of survivors within the first year. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated cardiovascular benefits in established heart failure, but their role in preventing new-onset heart failure post-myocardial infarction remains uncertain. We aimed to evaluate the efficacy and safety of SGLT2 inhibitors for heart failure prevention in post-myocardial infarction patients without established heart failure. Methods We searched PubMed (n = 284), Embase (n = 1,735), Cochrane Central (n = 440), and Scopus (n = 853) from inception to January 15, 2025, for randomized controlled trials comparing SGLT2 inhibitors with placebo in adults with acute myocardial infarction but no established heart failure, with a minimum 6-month follow-up. The primary outcome was heart failure hospitalization. We performed random-effects meta-analysis with the Hartung-Knapp adjustment using R version 4.3.0. We conducted trial sequential analysis and Bayesian sensitivity analyses. This review was registered with PROSPERO (CRD420251080192). Results Three trials enrolled 11,015 patients (EMPACT-MI: n = 6,522; DAPA-MI: n = 4,017; EMMY: n = 476). Two trials (n = 10,539) provided time-to-event data for heart failure hospitalization. SGLT2 inhibitors showed a 22% reduction in heart failure hospitalization (HR 0.78, 95% CI 0.54–1.13), though this did not reach conventional statistical significance (p = 0.075) with the Hartung-Knapp method. Sensitivity analysis using fixed-effect modeling yielded HR 0.78 (95% CI 0.63–0.97, p = 0.028). No heterogeneity was observed (I²=0%). Trial sequential analysis indicated only 1.7% of required information size has been accrued. Bayesian analysis indicated 97.7% probability of benefit (posterior HR 0.814, 95% CrI 0.666–0.996). SGLT2 inhibitors were well-tolerated with no excess serious adverse events (18.7% vs 17.2%) or diabetic ketoacidosis in non-diabetic patients. Conclusions SGLT2 inhibitors showed a consistent but statistically non-significant reduction in heart failure hospitalization following myocardial infarction in patients without established heart failure. While the direction and magnitude of effect align with established benefits in other populations, larger trials are needed to confirm these findings and establish SGLT2 inhibitors' role in post-myocardial infarction care.