Early SGLT2 Inhibitor Therapy in Acute Coronary Syndrome: Mitigating Adverse Remodeling in High-Risk Phenotypes—A Real-World Study

Background and Objectives: SGLT2 inhibitors are foundational in heart failure therapy, yet their impact on left ventricular (LV) remodeling immediately following acute coronary syndrome (ACS) remains less defined. This study evaluated the association between early SGLT2 inhibitor initiation and structural recovery in a real-world post-ACS cohort. Materials and Methods: We conducted a retrospective observational study including 238 revascularized ACS patients, stratified into an SGLT2 inhibitor group (n = 71) and a control group (n = 167). Changes in LV ejection fraction (LVEF) and indexed LV mass (LVMi) were assessed by echocardiography at baseline and follow-up (mean 286 days). Multivariable regression models were adjusted for baseline imbalances and tested for interactions with diabetes status. Results: A significant “confounding by indication” was observed; the SGLT2 group presented a high-risk phenotype with higher diabetes prevalence (56.3% vs. 25.7%, p < 0.001), lower baseline LVEF (38.3% vs. 43.3%), and greater hypertrophy. After adjustment, statistical independence was attenuated by baseline severity, yet the SGLT2 group achieved follow-up structural outcomes comparable to lower-risk controls. Interaction analysis indicated these trends were consistent regardless of diabetes status (p > 0.05). Conclusions: In this high-risk ACS population, early SGLT2 inhibitor therapy was associated with stabilization of cardiac structure. Despite a profound baseline disadvantage, the recovery trajectory effectively aligned with that of a lower-risk population, highlighting a clinically relevant pattern of structural stabilization consistent across metabolic subgroups.