Certain Inflammation Inhibition Does Not Reduce Cardiovascular Risks

Low-dose methotrexate does not reduce risk for atherosclerotic or cardiovascular events, according to study results.

To reach this conclusion, the researchers conducted a randomized, double-blind trial of low-dose methotrexate (at a target dose of 15 to 20 mg weekly) or matching placebo.

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There were 4786 participants who had had a myocardial infarction or multivessel coronary disease and who also had either type 2 diabetes or the metabolic syndrome. Each participant was assigned to take folate, 1 mg, daily.

After a median follow-up of 2.3 years, low-dose methotrexate did not have reduce levels of interleukin-1β, interleukin-6, or C-reactive protein.

Among those in the methotrexate group, 201 participants achieved the primary end point of a composite of nonfatal myocardial infarction, nonfatal stroke, cardiovascular death, or hospitalization for unstable angina that led to urgent revascularization (incidence rate of 4.13 per 100 person-years). The same primary endpoint was met by 207 participants in the placebo group (incidence rate 4.31 per 100 person-years).

Methotrexate was also associated with elevations in liver-enzyme levels, reductions in leukocyte counts and hematocrit levels, and a higher incidence of non–basal-cell skin cancers than placebo.

—Colleen Murphy

Reference:

Ridker PM, Everett BM, Pradhan A, et al. Low-dose methotrexate for the prevention of atherosclerotic events [published online November 10, 2018]. N Engl J Med. https://www.nejm.org/doi/10.1056/NEJMoa1809798.