6/28/23, 12:09 AM CIRT Pathway Feedback Search Clinical Topics Home Studies CIRT CIRT Disease Disease Coronary artery disease Diabetes mellitus type 2 Trial question What is the role of low-dose methotrexate in patients with previous MI or MVCAD? Study design Multi-center Double blinded RCT Population Characteristics of study participants 19.0% female N = 4786 81.0% male 4786 patients (898 female, 3888 male) Inclusion criteria: patients with previous MI or multivessel CAD and either T2DM or metabolic syndrome Key exclusion criteria: history of chronic infection, tuberculosis, pulmonary fibrosis, alcohol abuse, hepatic or renal dysfunction and women of childbearing potential Interventions N=2391 low-dose methotrexate (15 to 20 mg weekly, with 1 mg folate daily) N=2395 placebo (matching tablet weekly, with 1 mg folate daily) Primary outcome Incidence of nonfatal MI, nonfatal CVA, CV death, or hospitalization for UA requiring urgent revascularization 4.3/100 py 4.31 4.13 3 2/100 py https://web.pathway.md/studies/recNLBmLBV0zB52Ob 1/2 6/28/23, 12:09 AM 3.2/100 py CIRT Pathway 2.2/100 py 1.1/100 py No significant difference 0.0/100 py Low-dose methotrexate Placebo No significant difference in the incidence of nonfatal MI, nonfatal CVA, CV death, or hospitalization for UA requiring urgent revascularization (4.13 /100 py vs. 4.31 /100 py; HR 0.96, 96% CI 0.79 to 1.16) Secondary outcomes No significant difference in the incidence of nonfatal MI, nonfatal CVA, or CV death (3.46 /100 py vs. 3.43 /100 py; HR 1.01, 95% CI 0.82 to 1.25) Safety outcomes No significant differences in serious adverse events, including bleeding and infection. Leukopenia, elevated liver enzymes and increased incidence of non-basal-cell skin cancer was noted in methotrexate group than in placebo. Conclusion In patients with previous MI or multivessel CAD and either T2DM or metabolic syndrome, low- dose methotrexate was not superior to placebo with respect to the incidence of nonfatal MI, nonfatal CVA, CV death, or hospitalization for UA requiring urgent revascularization. Reference Ridker PM, Everett BM, Pradhan A et al. Low-Dose Methotrexate for the Prevention of Atherosclerotic Events. N Engl J Med. 2019 Feb 21;380(8):752-762. Open reference URL https://web.pathway.md/studies/recNLBmLBV0zB52Ob 2/2