Risk of Gastrointestinal Bleeding in Patients Taking Non–Vitamin K Antagonist Oral Anticoagulants: A Systematic Review and Meta-analysis

  • Author Footnotes
    a Authors share co-first authorship.
    Corey S. Miller
    Footnotes
    a Authors share co-first authorship.
    Affiliations
    Internal Medicine Residency Training Program, Department of Medicine, McGill University, Montreal, Canada
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  • Author Footnotes
    a Authors share co-first authorship.
    Alastair Dorreen
    Footnotes
    a Authors share co-first authorship.
    Affiliations
    Division of Gastroenterology, Dalhousie University, Halifax, Nova Scotia, Canada
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  • Myriam Martel
    Affiliations
    Department of Epidemiology and Biostatistics and Occupational Health, McGill University, Montreal, Canada
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  • Thao Huynh
    Affiliations
    Division of Cardiology, McGill University Health Center, McGill University, Montreal, Canada
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  • Alan N. Barkun
    Correspondence
    Reprint requests Address requests for reprints to: Alan N. Barkun, MD, Division of Gastroenterology, McGill University Health Center, Montreal General Hospital Site, 1650 Cedar Avenue, Room D7-346, Montreal, Canada H3G 1A4. fax: (514) 834-8531.
    Affiliations
    Department of Epidemiology and Biostatistics and Occupational Health, McGill University, Montreal, Canada

    Division of Gastroenterology, McGill University Health Center, McGill University, Montreal, Canada
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  • Author Footnotes
    a Authors share co-first authorship.
Published:April 27, 2017DOI:https://doi.org/10.1016/j.cgh.2017.04.031

      Background & Aims

      Non–vitamin K antagonist oral anticoagulants (NOACs) are convenient and effective in the prevention and treatment of venous thromboembolism and the prevention of stroke in patients with atrial fibrillation. However, these drugs have been associated with an increased risk of gastrointestinal (GI) bleeding. We conducted a systematic review and meta-analysis to determine the risk of GI bleeding in patients receiving these drugs.

      Methods

      We searched the EMBASE, Medline, Cochrane, and ISI Web of knowledge databases through January 2016 for randomized trials that compared NOACs with conventional anticoagulants for approved indications. We conducted a meta-analysis, reporting odds ratios (ORs) with 95% confidence intervals (CIs). The primary outcome was major GI bleeding. Secondary outcomes included clinically relevant nonmajor bleeding and upper and lower GI bleeding. We performed a priori subgroup analyses by individual drug.

      Results

      Our analysis included a total of 43 randomized trials, comprising 166,289 patients. There was no difference between NOACs and conventional anticoagulants in the risk of major bleeding (1.5% vs 1.3%, respectively; OR, 0.98; 95% CI, 0.80–1.21), clinically relevant nonmajor bleeding (0.6% vs 0.6%, respectively; OR, 0.93; 95% CI, 0.64–1.36), upper GI bleeding (1.5% vs 1.6%, respectively; OR, 0.96; 95% CI, 0.77–1.20), or lower GI bleeding (1.0% vs 1.0%, respectively; OR, 0.88; 95% CI, 0.67–1.15). Dabigatran (2.0% vs 1.4%, respectively; OR, 1.27; 95% CI, 1.04–1.55) and rivaroxaban (1.7% vs 1.3%, respectively; OR, 1.40; 95% CI, 1.15–1.70) were associated with increased odds of major GI bleeding compared with conventional anticoagulation, whereas no difference was found for apixaban (0.6% vs 0.7%, respectively; OR, 0.81; 95% CI, 0.64–1.02) or edoxaban (1.9% vs 1.6%, respectively; OR, 0.93; 95% CI, 0.78–1.11). These subgroup findings were not observed in other sensitivity analyses.

      Conclusions

      In a systematic review and meta-analysis, we found risk of major GI bleeding to be similar between NOACs and conventional anticoagulation. Dabigatran and rivaroxaban, however, may be associated with increased odds of major GI bleeding. Further high-quality studies are needed to characterize GI bleeding risk among NOACs.

      Keywords

      Abbreviations used in this paper:

      AF (atrial fibrillation), CI (confidence interval), CRNM (clinically relevant nonmajor), OR (odds ratio), GI (gastrointestinal), HR (hazard ratio), NOAC (novel oral anticoagulant), RCT (randomized controlled trial), VTE (venous thromboembolism)
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      • Issue Highlights
        Clinical Gastroenterology and HepatologyVol. 15Issue 11
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