AHA 2018 — Low-dose methotrexate does not confer preventive benefit in atherosclerosis


  • Hao Cheng, MD
  • Conference Reports
Access to the full content of this site is available only to registered healthcare professionals. Access to the full content of this site is available only to registered healthcare professionals.

Takeaway

  • Low-dose methotrexate confers no benefit to cardiac events for patients with stable atherosclerotic disease.

Why this matters

  • Inflammation is causally related to atherothrombosis.
  • Canakinumab, a monoclonal antibody, resulted in a lower rate of cardiovascular events than placebo in a previous randomized trial (CANTOS).
  • This study determines whether low-dose methotrexate confers a similar benefit.

Study design

  • Randomized, double-blind trial of low-dose methotrexate (at a target dose of 15-20 mg weekly) vs placebo.
  • Patients were included if they had previous myocardial infarction or multivessel coronary disease who additionally had either type 2 diabetes or the metabolic syndrome.
  • Primary endpoints were a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death as well as hospitalization for unstable angina that led to urgent revascularization.

Key results

  • 4786 patients were randomly assigned with a median follow-up of 2.3 years.
  • Methotrexate did not result in lower interleukin-1β, interleukin-6, or C-reactive protein levels than placebo.
  • The original primary endpoint occurred in 170 patients in the methotrexate group and in 167 in the placebo group (incidence rate, 3.46 vs 3.43 per 100 person-years; HR [CI 95%] = 1.01 [0.82-1.25]).
  • Methotrexate was associated with:
    • Elevations in liver-enzyme levels, P<.001.>
    • Reductions in leukocyte counts and hematocrit levels, P<.001.>
    • Higher incidence of non–basal-cell skin cancers, P=.002.

Limitations

  • Lower inflammatory markers compared with CANTOS study.

Expert comment

  • "How could these two studies [CIRT and CANTOS] be different? Well . . . the HsCRP (inflammatory risk) in CIRT is 1.5 mg. In CANTOS, it's 4.2 mg... In addition, the mean LDL-C was reduced to 68 mg/dL in CIRT whereas the group in CANTOS had a mean of 82 mg/dL. So the group in CANTOS is arguably higher risk and has a greater presence of [inflammation]."  Sidney C. Smith, Jr., MD, Professor of Medicine, University of North Carolina.

Please confirm your acceptance

To gain full access to GPnotebook please confirm:

By submitting here you confirm that you have accepted Terms of Use and Privacy Policy of GPnotebook.

Submit