Abstract 13194: The Effects of Methotrexate Therapy on Myocardial Infarction With ST-Segment Elevation (TETHYS Trial)
Introduction: Acute myocardial infarction provokes inflammatory activation. Methotrexate is one drug that has been shown to have anti-ischemic effects in experimental studies.
Hypothesis: Methotrexate could reduce inflammation and the ischemia area in acute myocardial infarction
Methods: We randomly assigned patients with myocardial infarction with ST-segment elevation to receive either methotrexate (0.05 mg/kg bolus followed by 0.05 mg/kg/h for 6 h) or matching placebo (riboflavin sodium phosphate 0.1%, in order to preserve double-blinding) at a ratio of 1:1. Patients in both groups were given a 5mg single dose of folic acid. The primary endpoint was infarct size, determined by the area under the curve (AUC) for creatine kinase (CK) release. Secondary endpoints were AUC of 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); TIMI frame count; Killip score; mortality and reinfarction incidence. The safety endpoint was the incidence of adverse reactions.
Results: We included 84 patients. The AUC of CK was 78,861.00 in the methotrexate group and 68,088.00 in the placebo group (P=0.10). Patients given methotrexate and placebo exhibited, respectively, AUC for CK-MB of 9,803.40 and 8,037.00 (P=0.42); AUC for troponin I of 3,691.11 and 2,132.63 (P=0.09); peak CK of 2,806.00 and 2,147.00 (P=0.05), peak CK-MB of 516.00 and 462.25 (P=0.25) and peak troponin I of 121.00 and 85.05 (P=0,06). At 3 months, LVEF was lower in patients who received methotrexate (48.97±14.09%) than in patients given placebo (56.37±9.97%) (P=0.01). There were no differences in hsCRP, ESR, BNP, Killip scores or TIMI frame count. There were also no differences in reinfarction or mortality rates or in incidence of side effects, with the exception of higher median serum glutamic-pyruvic transaminase (SGPT) levels in the methotrexate group.
Conclusions: Methotrexate did not reduce infarction size and worsened LVEF at 3 months.
Author Disclosures: D.M. Moreira: None. R.L. da Silva: None. M.E. Lueneberg: None. T. Fattah: None. C.A. Gottschall: None.
- © 2015 by American Heart Association, Inc.