Abstract
Background and Objectives: This systematic review and meta-analysis aims to evaluate whether the benefits of sodium-glucose co-transporter-2 (SGLT2) inhibitors on cardiovascular outcomes extend when initiated in patients with acute coronary syndrome (ACS), regardless of diabetic status. Materials and Methods: PubMed, Embase, and the Cochrane Library were searched from 2015 up to July 2025, according to PRISMA 2020 guidelines. Eligible studies were randomized controlled trials (RCTs) and observational studies comparing SGLT2 inhibitors with controls in post-ACS patients. Articles without full-text data for extraction, with unavailable outcome data or evaluating patients with stable coronary artery disease (CAD) were excluded. Primary outcomes were all-cause and cardiovascular (CV) mortality. Secondary outcomes included recurrent myocardial infarction (MI), rehospitalization for ACS, revascularization and stroke. Meta-analysis was conducted using the R statistical software (Version 4.5.1). Subgroup analysis was performed by study design to evaluate outcomes in type 2 diabetes mellitus (T2DM) populations. Risk of bias was assessed using the Cochrane Risk of Bias (RoB) 2.0 and Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) tools. Certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Results: A total of 16 studies were included in the meta-analysis, encompassing over 130,000 patients. Initiation of SGLT2 inhibitors after ACS was associated with a significant reduction in the primary outcome of all-cause mortality [hazard ratio (HR) = 0.77; (95% confidence interval (CI): 0.67-0.89)] and CV mortality [HR = 0.83; (95% CI: 0.70-0.99)]. In subgroup analyses, patients with T2DM experienced a significant reduction in all-cause mortality [HR = 0.73, (95% CI: 0.62-0.86)] and recurrent MI [HR = 0.83, (95% CI: 0.69-0.99)]. Conclusions: Initiation of SGLT2 inhibitors after ACS is associated with a significant reduction in all-cause and CV mortality. Subgroup analysis further demonstrated a reduction in all-cause mortality and recurrent myocardial infarction among patients with T2DM, while in patients without diabetes, no significant effects were observed. Although evidence certainty ranged from low to moderate and large RCTs are still ongoing, these findings support the early introduction of SGLT2 inhibitors in eligible patients with T2DM following ACS, pending confirmation by large, prospective clinical trials.