Methotrexate and Cardiovascular Protection: Current Evidence and Future Directions

Arduino Mangoni, Angelo Zinellu, Salvatore Sotgia, Ciriaco Carru, Gian Erre

    Research output: Contribution to journalArticlepeer-review

    11 Citations (Scopus)


    Patients with autoimmune rheumatic conditions, particularly rheumatoid arthritis, have an increased cardiovascular risk when compared with the general population. Methotrexate is a relatively old, yet effective, immunomodulatory drug for the management of autoimmune and chronic inflammatory disorders, such as rheumatoid arthritis, particularly in terms of symptom control, quality of life, and disease progression. Recent meta-analyses have also shown that methotrexate treatment is associated with a lower risk of cardiovascular events when compared with other disease-modifying antirheumatic drugs. This suggests that methotrexate might exert specific protective effects against atherosclerosis and thrombosis. This mini-review discusses the mechanisms associated with the increased cardiovascular risk in rheumatoid arthritis, the pharmacokinetics and pharmacodynamics of methotrexate, the available evidence on the in vitro and in vivo effects of methotrexate on modifiable cardiovascular risk factors, and suggestions for future research directions.

    Original languageEnglish
    Pages (from-to)1-12
    Number of pages12
    JournalClinical Medicine Insights: Therapeutics
    Publication statusPublished - 2017


    • Cardiovascular disease
    • Cardiovascular risk factors
    • Inflammation
    • Methotrexate
    • Rheumatoid arthritis


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