Cardiovascular outcomes of SGLT2 inhibitors across the spectrum of myocardial infarction: A systematic review and meta-analysis.

Aims

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) help in heart failure (HF), but their benefit after acute myocardial infarction is unclear. This meta-analysis assesses their impact on mortality and heart failure hospitalization post-acute myocardial infarction (AMI) and identifies which patients benefit most.

Methods

Four databases were searched through August 2025 for randomized controlled trials (RCTs) and matched studies comparing SGLT2i with control post-AMI. PRIMARY OUTCOMES all-cause death and hospitalization for heart failure (HHF); secondary: major adverse cardiovascular events (MACE), cardiovascular (CV) death, stroke and recurrent myocardial infarction (MI). Subgroups and meta-regression examined timing, diabetes, follow-up, design, SGLT2i type and baseline HF/diabetes.

Results

Fifteen studies including 117 096 patients (58 613 SGLT2i vs. 58 483 control) were included. A total of 117 096 patients contributed to the all-cause mortality analysis (OR 0.78, 95% CI 0.67-0.90), whereas 116 992 patients across 14 studies contributed to the HHF analysis (OR 0.74, 95% CI 0.63-0.88). All-cause mortality was significantly lower in PSM observational studies (OR 0.64, 95% CI 0.61-0.67), whereas the reduction did not reach statistical significance in RCTs (OR 0.87, 95% CI 0.76-1.01), with a significant interaction by study design. HHF reduction occurred with both early and delayed initiation; dapagliflozin and empagliflozin were similarly effective. MACE was significantly lower with SGLT2i, but CV death, recurrent MI and stroke did not differ. Baseline HF or diabetes showed no association with primary outcomes.

Conclusions

SGLT2i reduced HHF after MI, but this benefit should be interpreted cautiously because of small-study effects and possible publication bias. The all-cause mortality benefit is driven by observational studies; RCTs show a favourable but nonsignificant trend.