Protective effect of methotrexate in patients with rheumatoid arthritis and cardiovascular comorbidity.

Rheumatoid arthritis (RA) is associated with an increased risk of premature mortality, predominantly due to increased cardiovascular disease (CVD). Systemic inflammation has been established as one of the primary drivers of accelerated atherosclerosis in RA, though other traditional and disease-specific risk factors also contribute. There is evidence that methotrexate, considered a mainstay of therapy for RA, can ameliorate some of this excess CVD risk, an effect that has not been seen consistently with other disease-modifying antirheumatic drugs. The cardioprotective action of methotrexate may occur through reducing systemic inflammation and by directly affecting some of the cellular mechanisms that lead to atherosclerosis. On the basis of this evidence, there are ongoing trials of low-dose methotrexate in patients from the general population with CVD but who do not have RA. Methotrexate reduces the overall CVD burden in patients with RA. With earlier treatment of RA and earlier use of methotrexate it is possible that we may have the capability to radically change patients' long-term CVD risk.