Empagliflozin in STEMI Patients: A Randomized Controlled Trial on Left Ventricular Recovery and Cardiovascular Outcomes.

Abstract

Sodium-glucose cotransporter 2 (SGLT2) inhibitors provide cardiovascular benefits in diabetes, but their role in the acute post-myocardial infarction (MI) setting is uncertain. This study evaluated the association of empagliflozin with left ventricular ejection fraction (LVEF) recovery and major adverse cardiac events (MACE) in patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). In a single-center, double-blind, randomized, placebo-controlled trial, patients with STEMI were randomized to empagliflozin 10 mg or placebo daily for 40 days. The primary endpoint was change in left ventricular ejection fraction (LVEF) from baseline to day 40, with sample size calculated a priori based on data from the EMMY trial (minimum 27 per group; 53 per group enrolled). Major adverse cardiac events (MACE)-defined as cardiovascular death, myocardial infarction, or stroke-were assessed as a secondary exploratory endpoint. A total of 117 patients were randomized (59 empagliflozin, 58 placebo), of whom 106 completed follow-up and were analyzed (53 per group). Empagliflozin was associated with significantly greater LVEF recovery at day 40 (mean increase: 7.35% ± 6.11% versus 2.96% ± 5.49%; mean difference 4.39%, 95% CI 2.09-6.70%; P = 0.000272), which remained significant after adjustment for baseline LVEF, age, sex, and diabetes status (adjusted difference: 3.44%, 95% CI 1.22-5.66%; P = 0.003; Cohen's d = 0.756). The benefit was numerically greater in younger and nondiabetic patients, though no subgroup interaction reached significance after multiplicity correction. MACE did not differ significantly between groups (3.8 versus 7.5%; P = 0.68), with no recurrent MI or stroke in either group. Adverse events were rare and comparable, with no diabetic ketoacidosis, amputation, or acute kidney injury observed. In this preliminary single-center trial, empagliflozin was associated with significantly greater LVEF recovery in patients with STEMI after PCI, with effects robust to covariate adjustment, and without increasing adverse events. Although MACE was not significantly reduced-as expected given the study was not powered for hard clinical events-the LVEF improvement represents a promising early prognostic signal. These findings are applicable to lower-risk patients with STEMI with successful reperfusion and may not generalize to higher-risk patients with failed PCI or hemodynamic compromise. Larger, adequately powered, long-term multicenter trials are needed to confirm clinical benefits. Registered at the Iranian Registry of Clinical Trials identifier no. IRCT20220809055645N7.