MethotrexaTE THerapy in ST-Segment Elevation MYocardial InfarctionS: A Randomized Double-Blind, Placebo-Controlled Trial (TETHYS Trial)

Purpose:Methotrexate is an anti-inflammatory drug that has been shown to have anti-ischemic effects. Our aim was to evaluate if methotrexate could reduce infarct size in patients with ST-segment elevation myocardial infarction (STEMI).Methods:We randomly assigned patients with STEMI to receive either methotrexate or placebo. Primary outcome was infarct size determined by calculating the area under the curve (AUC) for creatine kinase (CK) release. Secondary outcomes were AUC of CK MB (CK-MB) and AUC of troponin I; peak CK, peak CK-MB, and troponin I; B-type natriuretic peptide (BNP) level, high-sensitivity C-reactive protein (hsCRP) result, and erythrocyte sedimentation rate (ESR); left ventricular ejection fraction (LVEF); thrombolysis in myocardial infarction (TIMI) frame count; Killip score; mortality and reinfarction incidence; and incidence of adverse reactions.Results:We included 84 patients. Median AUC of CK was 78 861.0 in the methotrexate group and 68 088.0 in the placebo group (P = .10). Patients given methotrexate and placebo exhibited, respectively, median AUC for CK-MB of 9803.4 and 8037.0 (P = .42); median AUC for troponin of 3691.1 and 2132.6 (P = .09); peak CK of 2806.0 and 2147.0 (P = .05); peak CK-MB of 516.0 and 462.3 (P = .25); and peak troponin of 121.0 and 85.1 (P = .06). At 3 months, LVEF was lower in patients who received methotrexate (49.0% 14.1%) than in patients given placebo (56.4% +/- 10.0%; P = .01). There were no differences in hsCRP, ESR, BNP, Killip scores, TIMI frame count, reinfarction, and mortality rates. There was a higher median serum glutamic-pyruvic transaminase levels in the methotrexate group.Conclusion: Methotrexate did not reduce infarction size and worsened LVEF at 3 months.