Intravenous LDE-Methotrexate in Anterior ST-Elevation Myocardial Infarction: Effects on Left Ventricular Remodeling, Infarct Size, and Safety Profile — A Randomized, Double-Blind, Placebo-Controlled Study

Abstract Background: Anterior ST-segment elevation myocardial infarction (STEMI) is associated with extensive necrosis, adverse left ventricular (LV) remodeling, and increased mortality despite optimal reperfusion therapy. Lipid nanoemulsion formulation of methotrexate (LDE-MTX) has been proposed as an anti-inflammatory and anti-proliferative therapy that could modulate post-infarction inflammation and remodeling. This study evaluates the efficacy and safety of intravenous LDE-MTX administered early in anterior STEMI. Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, 240 patients with first anterior STEMI undergoing primary percutaneous coronary intervention (PCI) were randomized 1:1 to receive intravenous LDE-MTX or placebo within 6 hours of symptom onset. Primary endpoints were change in LV end-systolic volume index (LVESVI) and infarct size at 6 months measured by cardiac magnetic resonance imaging (CMR). Secondary endpoints included heart failure hospitalization, major adverse cardiovascular events (MACE), and safety outcomes. Results: LDE-MTX was associated with a significantly smaller increase in LVESVI and reduced infarct size at 6 months compared to placebo. The incidence of MACE and heart failure was lower in the LDE-MTX group. Adverse events were comparable between groups, with no significant increase in hepatic, renal, or hematologic toxicity. Conclusions: Early intravenous administration of LDE-MTX in anterior STEMI patients was safe and resulted in favorable effects on LV remodeling and infarct size, suggesting potential as an adjunctive therapy to reperfusion.