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A Meta-Analysis of Randomized Controlled Trials of the Risk of Bleeding With Apixaban Versus Vitamin K Antagonists

  • Lahoud Touma
    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

    Department of Epidemiology, Biostatistics, and Occupational Health, 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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  • Maria Eberg
    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

    Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada

    Division of Cardiology, Jewish General Hospital/McGill University, Montreal, Quebec, Canada
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Published:December 01, 2014DOI:https://doi.org/10.1016/j.amjcard.2014.11.039

      Highlights

      • The results are based on data from 24,435 patients across 5 trials.
      • Apixaban is associated with a lower risk of bleeding compared with vitamin K antagonists (VKAs).
      • Apixaban may be associated with reduced all-cause mortality compared with VKAs.
      • Apixaban may represent an effective and safe alternative to the standard VKA therapy.
      Apixaban is one of the new oral anticoagulants, which is prescribed as an alternative to vitamin K antagonists (VKAs). Concerns regarding its bleeding profile persist and require further evaluation. Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) to compare the risks of bleeding and all-cause mortality between apixaban and VKAs. The MEDLINE, EMBASE, and Cochrane Library of Clinical Trials databases were systematically searched for RCTs comparing the risks of bleeding and all-cause mortality of apixaban (2.5 or 5 mg twice daily) with those of VKAs. We included RCTs conducted in adults and published in English or French. Data were pooled across RCTs using random-effects meta-analytical models. Our systematic search identified 5 RCTs meeting our inclusion criteria (n = 24,435). They included patients with atrial fibrillation (n = 18,358), total knee replacement surgery (n = 458), and venous thromboembolism (n = 5,619). Data pooled across RCTs revealed that apixaban was associated with reduced risks of any bleeding (relative risk [RR] 0.73, 95% confidence interval [CI] 0.59 to 0.90) and a composite of major or clinically relevant nonmajor bleeding (RR 0.60, 95% CI 0.40 to 0.88). Apixaban was also associated with a lower risk of intracranial bleeding (RR 0.42, 95% CI 0.31 to 0.58) whereas analyses of major and minor bleeding were inconclusive. Moreover, apixaban was associated with decreased all-cause mortality (RR 0.89, 95% CI 0.81 to 0.99) although this finding was driven by the results of the ARISTOTLE trial. In conclusion, our meta-analysis found that apixaban is associated with a lower risk of bleeding than VKAs, providing some reassurance regarding its safety.
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