Methotrexate Reduces Cardiovascular Risk in Elderly-Onset Rheumatoid Arthritis

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Researchers evaluated the associations between time-varying methotrexate use and risk for cardiovascular events in patients with rheumatoid arthritis.

Elderly patients with rheumatoid arthritis (RA) continuously taking methotrexate over the course of 12 months showed a 20% decrease in their risk for cardiovascular events compared with patients who did not take any methotrexate over the previous year, according to a study published in The Journal of Rheumatology.  

In this cohort study, researchers examined the effect of time-varying RA treatment on the risk for cardiovascular events in patients older than 66 years. Data on patients, diagnoses, and procedures were taken from Ontario Health Insurance Plan (OHIP) Claims History Database and analyses were limited to patients >66 years with RA for whom there were full prescription drug histories available (n=23,994). Associations between time-varying methotrexate use and time to cardiovascular events, controlling for other risk factors, were found using multivariable Cox regression models. The cumulative duration of methotrexate use over the first year, the previous year, and the entire follow-up period were assessed with alternative models. Investigators also assessed how the strength of these associations may have varied over time.

During the 115,453 patient-years of total follow-up time, 13.7% of patients (n=3294) experienced a cardiovascular event (28.5 events per 1000 PY; 95% CI, 27.6–29.5). Using methotrexate continuously over the prior year was associated with a 20% reduction in risk for cardiovascular events compared with those who did not use methotrexate in the past 12 months (adjusted hazard ratio [HR], 0.79; 95% CI, 0.70–0.88; <.0001), and this association remained reasonably constant thereafter, with a minor trend of weakening over time. Greater use of methotrexate in the first cohort year was also shown to be protective (HR, 0.84; 95% CI, 0.72-0.96; =.0048), although the effect did decrease with increasing follow- up. There was no clear association between longer use of methotrexate and risk of cardiovascular events (HR, 0.98; 95% CI, 0.95-1.01; =.1441) throughout the entire follow-up period.

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Study investigators conclude, “Our epidemiological evidence supports clinical recommendations that patients with RA should initiate [methotrexate] treatment early, with appropriate continuation to control disease over time.”


Widdifield J, Abrahamowicz M, Paterson JM, et al. Associations between methotrexate use and the risk of cardiovascular events in patients with elderly-onset rheumatoid arthritis [published online December 1, 2018]. J Rheumatol. doi: 10.3899/jrheum.180427