CIRT
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
81.0% male
N = 4786
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
4.13
4.31
4.3/100 py
3.2/100 py
2.2/100 py
1.1/100 py
0.0/100 py
Low-dose
methotrexate
Placebo
No significant
difference ↔
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.
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