ReviewSystematic Review and Meta-Analysis of Methotrexate Use and Risk of Cardiovascular Disease
Section snippets
Methods
The Meta-Analysis of Observational Studies in Epidemiology guidelines6 were used as a reference for all stages of design, implementation, and reporting of this systematic review and meta-analysis.
We searched for all clinical trials or observational studies (prospective or retrospective or case-control studies) in which adults received methotrexate, the duration of follow-up was ≥3 months, and reported effect estimates on occurrence of “hard” CVD events (myocardial infarction [MI], coronary
Results
The 10 identified investigations included 8 prospective and 2 retrospective cohort studies in America (n = 6) and Europe (n = 4) and included 66,334 subjects in whom 6,235 CVD events were identified10, 13, 14, 15, 16, 17, 18, 19, 20, 21 (Table 1). We did not identify any randomized controlled trials that assigned methotrexate and assessed the occurrence of “hard” CVD events. One study19 provided 2 separate estimates for patients receiving methotrexate with RA and polyarthritis as the underlying
Discussion
In this meta-analysis of observational studies, methotrexate use among patients with systemic inflammation (mainly RA) was associated with 21% lower CVD risk, with little evidence of between-study heterogeneity. Similar inverse associations were observed for MI and stroke separately.
In general, findings in each of the sensitivity analyses performed were consistent and similar to the overall pooled estimate. For a few sources of heterogeneity, which in fact reflect potentially important study
Acknowledgment
We thank Vokko P. van Halm for providing additional unpublished data.
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This study was supported by Grant RC2 HL101816 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland, and Grant R01 HL080644 from the National Institutes of Health, Bethesda, Maryland.
Dr. Ridker is listed as a coinventor on patents held by Brigham and Women's Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease.