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Methotrexate and Risk of Cardiovascular Disease

      The systematic review and meta-analysis by Micha et al
      • Micha R.
      • Imamura F.
      • Wyler von Ballmoos M.
      • Solomon D.H.
      • Hernán M.A.
      • Ridker P.M.
      • Mozaffarian D.
      Systematic review and meta-analysis of methotrexate use and risk of cardiovascular disease.
      addresses a clinically important issue. Methotrexate is the most common disease-modifying antirheumatic drug prescribed in patients with rheumatoid arthritis (RA).
      • Scott D.L.
      • Wolfe F.
      • Huizinga T.W.
      Rheumatoid arthritis.
      Unfortunately, the validity of the review is compromised by misclassification of the epidemiologic design of the original studies and by several errors in the effect sizes and related 95% confidence intervals (95% CIs) extracted from them.
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      References

        • Micha R.
        • Imamura F.
        • Wyler von Ballmoos M.
        • Solomon D.H.
        • Hernán M.A.
        • Ridker P.M.
        • Mozaffarian D.
        Systematic review and meta-analysis of methotrexate use and risk of cardiovascular disease.
        Am J Cardiol. 2011; 108: 1362-1370
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        • Wolfe F.
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      Linked Article

      • Systematic Review and Meta-Analysis of Methotrexate Use and Risk of Cardiovascular Disease
        American Journal of CardiologyVol. 108Issue 9
        • Preview
          Inflammation predicts risk for cardiovascular disease (CVD) events, but the relation of drugs that directly target inflammation with CVD risk is not established. Methotrexate is a disease-modifying antirheumatic drug broadly used for the treatment of chronic inflammatory disorders. A systematic review and meta-analysis of evidence of relations of methotrexate with CVD occurrence were performed. Cohorts, case-control studies, and randomized trials were included if they reported associations between methotrexate and CVD risk.
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      • Authors' Reply
        American Journal of CardiologyVol. 109Issue 12
        • Preview
          We appreciate Almalag and colleagues' interest in our systematic review and meta-analysis of the association between methotrexate (MTX) use and incident cardiovascular disease (CVD).1 Most of their questions arise from their errors during efforts to reproduce our findings. Their first, and relatively minor, error is their characterization of several of the cohort studies as retrospective. Although there is no single definition of what makes a cohort study prospective or retrospective, the key methodologic consideration is whether exposure status was assessed before or after the development of the outcome, which directly affects the likelihood of recall bias or exposure information bias.
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