Ridker PM, et al. - Given that inflammation is causally related to atherothrombosis and a lower rate of cardiovascular events has been reported with canakinumab treatment, researchers investigated if low-dose methotrexate could benefit similarly as an alternative approach to inflammation inhibition. According to results, there was no attenuation in interleukin-1β, interleukin-6, or C-reactive protein concentrations and no fewer cardiovascular events following treatment with low-dose methotrexate in this study population.

Methods

• This randomized, double-blind trial included 4,786 patients with previous myocardial infarction or multivessel coronary disease and either type 2 diabetes or the metabolic syndrome.
• Study participants were treated with low-dose methotrexate (at a target dose of 15 to 20 mg weekly) or matching placebo.
• All participants received 1 mg of folate daily.
• A composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death comprised the primary end point at the onset of the trial.
• Hospitalization for unstable angina that led to urgent revascularization was added to primary end point near the conclusion of the trial, but before unblinding.

Results

• A median follow-up of 2.3 years was performed, after which time the trial was stopped.
• Compared with placebo, no lowering of interleukin-1β, interleukin-6, or C-reactive protein levels was observed with methotrexate.
• The final primary end point occurred in 201 methotrexate-treated patients and 207 placebo-treated patients.
• In the methotrexate group and in the placebo group, the original primary end point occurred in 170 and 167 patients, respectively.
• Compared with placebo, the methotrexate-induced effects included elevations in liver-enzyme levels, reductions in leukocyte counts and hematocrit levels, and a higher incidence of non–basal-cell skin cancers.