Comparative Efficacy of GLP‐1 RAs Versus SGLT2 Inhibitors in Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention: A Multicenter Propensity Score‐Matched Real‐World Study

BACKGROUND: No head-to-head trials have directly compared GLP-1 receptor agonists (GLP‑1 RAs) and SGLT2 inhibitors (SGLT2is) in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI). AIMS: To compare short-, mid-, and long-term clinical outcomes of GLP-1 RAs versus SGLT2 inhibitors in adults with AMI undergoing PCI, using a multicenter propensity score-matched real-world cohort from the TriNetX US Collaborative Network. METHODS: This multicenter, retrospective cohort study used de-identified data from the TriNetX US Collaborative Network. Adults with AMI who underwent PCI and initiated either GLP‑1 RAs (n = 7201) or SGLT2is (n = 4252) within 14 days were included. One-to-one greedy nearest-neighbor propensity score matching (caliper 0.1) yielded balanced cohorts across > 50 covariates, resulting in 1752 patients per group. Kaplan-Meier and Cox models assessed mortality, heart failure, hospitalization, recurrent myocardial infarction (RMI), stroke, atrial fibrillation, major adverse cardiovascular events (MACE), acute kidney injury (AKI), and cardiac arrest. RESULTS: Compared with SGLT2is, GLP-1 RAs were associated with lower 1-year risks of acute heart failure (HR 0.415 [0.343-0.501]), all-cause hospitalization (HR 0.559 [0.495-0.631]), RMI (HR 0.799 [0.710-0.899]), stroke (HR 0.800 [0.667-0.959]), atrial fibrillation (HR 0.804 [0.693-0.932]), MACE (HR 0.788 [0.706-0.881]), and AKI (HR 0.534 [0.444-0.643]). At 30 days, absolute risk reduction was lower with GLP-1 RAs for acute heart failure (7.19% [5.66%-8.72%]) and all-cause hospitalization (16.61% [14.24%-18.98%]). All-cause mortality did not differ at 30 or 90 days but was lower at 1 year (HR 0.700 [0.507-0.967]). Cardiac arrest did not differ significantly. CONCLUSIONS: In this real-world, propensity score-matched study of patients with AMI undergoing PCI, GLP-1 RA initiation linked to lower risk of short- and long-term adverse outcomes than SGLT2i. These are observational findings needing confirmation in randomized trials.