Methotrexate and cardiovascular risk in rheumatic diseases:A comprehensive review

ABSTRACT

Introduction: Management of inflammatory rheumatic diseases has evolved based on improved treatment strategies and better management of comorbidities, specifically cardiovascular risk. Methotrexate is one of the first-line treatments in the management of inflammatory rheumatic diseases, but its cardiovascular effects are poorly understood. The purpose of this review is to assess the cardiovascular impact of methotrexate in inflammatory rheumatic disease.

Areas covered: Current knowledge about the mechanism of action of methotrexate on cardiovascular tissue is presented. A review of the literature in the Medline, Cochrane and Embase databases was performed. Current data about the cardiovascular effects of methotrexate in rheumatoid arthritis, psoriatic arthritis, and psoriasis are presented.

Expert opinion: Mechanism of action of methotrexate is based on the antagonism of purines. It reduces systemic inflammation and oxidative stress and improves the major cardiovascular risk factors. Methotrexate improves cardiovascular risk in rheumatoid arthritis, psoriasis and psoriatic arthritis, but the mechanisms involved are partially identified. Data are controversial regarding its effects on endothelial function and atherosclerosis. Conversely, in the general population and in patients with HIV infection, methotrexate does not modify cardiovascular outcomes. Thus, methotrexate only improves cardiovascular risk by reducing systemic inflammation, and should not be used to prevent cardiovascular events.

KEYWORDS:

• Methotrexate
• cardiovascular risk
• inflammatory rheumatic disease

Article highlights

• In RA, methotrexate is associated with a dose-dependent reduction in cardiovascular morbidity and mortality.

• In RA, the cardiovascular benefit of methotrexate is secondary to a reduction in systemic inflammation, insulin resistance and modification of lipid metabolism.

• In RA, data do not argue for a direct vascular effect of methotrexate.

• In Psoriatic Arthritis, the cardiovascular benefits of methotrexate are similar to those seen in RA.

• In the absence of inflammatory disease, such as post-myocardial infarction or in HIV patients, methotrexate does not reduce cardiovascular morbidity.

Declaration of interest

F. Verhoeven has declared receiving speaker fees/advisory board for Novartis, Amgen, MSD, Celgene, BMS and Roche Chugai.

-C. Prati has declared speaker fees/advisory board for Novartis, Lilly and Pfizer.

-D. Wendling has declared speaker fees/advisory board for AbbVie, BMS, MSD, Pfizer, Roche Chugai, Amgen, UCB, Novartis, Janssen, Lilly, Sandoz, Grunenthal, Mylan, Fresenius Kabi and Galapagos. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded