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Meta-Analysis of Randomized Controlled Trials on the Risk of Bleeding With Dabigatran

  • Benjamin J. Bloom
    Affiliations
    Division of Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital/McGill University, Montreal, Quebec, Canada

    Faculty of Medicine, McGill University, Montreal, Quebec, Canada
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  • Kristian B. Filion
    Affiliations
    Division of Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital/McGill University, Montreal, Quebec, Canada

    Faculty of Medicine, McGill University, Montreal, Quebec, Canada
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  • Renée Atallah
    Affiliations
    Division of Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital/McGill University, Montreal, Quebec, Canada
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  • Mark J. Eisenberg
    Correspondence
    Corresponding author: Tel: (514) 340-8222x3564; fax: (514) 340-7564.
    Affiliations
    Division of Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital/McGill University, Montreal, Quebec, Canada

    Faculty of Medicine, McGill University, Montreal, Quebec, Canada

    Division of Cardiology, Jewish General Hospital/McGill University, Montreal, Quebec, Canada
    Search for articles by this author
Published:December 26, 2013DOI:https://doi.org/10.1016/j.amjcard.2013.11.049
      Dabigatran is a univalent low-molecular-weight direct thrombin inhibitor that has been developed as an alternative to vitamin K antagonists (VKAs). However, uncertainty remains regarding dabigatran's safety profile with respect to bleeding. Our objective was to compare the risk of bleeding and all-cause mortality of dabigatran with that of VKAs in a systematic review and meta-analysis of randomized controlled trials (RCTs). We systematically searched MEDLINE, Embase, and the Cochrane Library of clinical trials to identify RCTs comparing the bleeding risk of dabigatran (150 mg twice daily) with that of VKAs. Included RCTs had treatment duration ≥90 days and were published in English or French. Data were meta-analyzed using random-effects models. Five RCTs (n = 20,332) were included in our systematic review. Study populations consisted of patients with atrial fibrillation (n = 18,615) and venous thromboembolism (n = 7,998). When data were pooled across the 4 RCTs (n = 17,466) without overlapping populations, dabigatran was not associated with an increased risk of major bleeding compared with VKAs (relative risk [RR] 0.92, 95% confidence interval [CI] 0.81 to 1.05). Dabigatran was associated with a decreased risk of intracranial bleeding (RR 0.40, 95% CI 0.27 to 0.59) but an increased risk of gastrointestinal bleeding (RR 1.51, 95% CI 1.23 to 1.84). Dabigatran was also associated with a trend toward decreased all-cause mortality (RR 0.90, 95% CI 0.80 to 1.01). In conclusion, results suggest that dabigatran has a favorable safety profile with respect to bleeding compared with VKAs.
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