Systematic review with meta-analysis: the risk of major gastrointestinal bleeding with non-vitamin K antagonist oral anticoagulants

作者：Caldeira D; Barra M; Ferreira A; Rocha A; Augusto A; Pinto F J; Costa J; Ferreira J J

来源：Alimentary Pharmacology and Therapeutics, 2015, 42(11-12): 1239-1249.

DOI：10.1111/apt.13412

<jats:title>Summary</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Gastrointestinal (<jats:styled-content style="fixed-case">GI</jats:styled-content>) bleeding is a common complication among anticoagulated patients. Non‐vitamin K antagonist oral anticoagulants (<jats:styled-content style="fixed-case">NOAC</jats:styled-content>s) are associated with increased risk of <jats:styled-content style="fixed-case">GI</jats:styled-content> (major and clinically relevant non‐major) bleeding. However, more information is needed regarding severe events.</jats:p></jats:sec><jats:sec><jats:title>Aim</jats:title><jats:p>To evaluate the risk of <jats:styled-content style="fixed-case">NOAC</jats:styled-content>s major <jats:styled-content style="fixed-case">GI</jats:styled-content> bleeding.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We searched for phase <jats:styled-content style="fixed-case">III</jats:styled-content> randomised clinical trials (<jats:styled-content style="fixed-case">RCT</jats:styled-content>) evaluating <jats:styled-content style="fixed-case">NOAC</jats:styled-content>s (apixaban, dabigatran, edoxaban and rivaroxaban) and reporting major <jats:styled-content style="fixed-case">GI</jats:styled-content> bleeding events, in <jats:styled-content style="fixed-case">MEDLINE</jats:styled-content>, Cochrane Library, Sci<jats:styled-content style="fixed-case">ELO</jats:styled-content> collection and Web of Science databases (July 2015). Meta‐analysis was performed to estimate risk ratio (<jats:styled-content style="fixed-case">RR</jats:styled-content>) and 95% confidence intervals (95% <jats:styled-content style="fixed-case">CI</jats:styled-content>s). Heterogeneity was assessed with the <jats:italic>I</jats:italic><jats:sup>2</jats:sup> test.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total of 23 studies were included. Among patients with atrial fibrillation, the risk of major <jats:styled-content style="fixed-case">GI</jats:styled-content> bleeding was not different between <jats:styled-content style="fixed-case">NOAC</jats:styled-content>s and vitamin K antagonists (<jats:styled-content style="fixed-case">VKA</jats:styled-content>) (<jats:styled-content style="fixed-case">RR</jats:styled-content> 1.08, 95% <jats:styled-content style="fixed-case">CI</jats:styled-content> 0.85–1.36, <jats:italic>I</jats:italic><jats:sup>2</jats:sup> = 78%; 5 <jats:styled-content style="fixed-case">RCT</jats:styled-content>s) or acetylsalicylic acid (<jats:styled-content style="fixed-case">RR</jats:styled-content> 0.78, 95% <jats:styled-content style="fixed-case">CI</jats:styled-content> 0.36–1.72; 1 <jats:styled-content style="fixed-case">RCT</jats:styled-content>). Similar results were found for patients undergoing orthopaedic surgery and those with venous thromboembolism. <jats:styled-content style="fixed-case">NOAC</jats:styled-content>s were not found to increase the risk compared to low‐molecular‐weight heparin (LWMH) alone (<jats:styled-content style="fixed-case">RR</jats:styled-content> 1.42, 95% <jats:styled-content style="fixed-case">CI</jats:styled-content> 0.55–3.71, <jats:italic>I</jats:italic><jats:sup>2</jats:sup> = 7%; 8 <jats:styled-content style="fixed-case">RCT</jats:styled-content>s), the sequential treatment with LMWH‐VKA (<jats:styled-content style="fixed-case">RR</jats:styled-content> 0.77, 95% <jats:styled-content style="fixed-case">CI</jats:styled-content> 0.49–1.21, <jats:italic>I</jats:italic><jats:sup>2</jats:sup> = 43%; 7 <jats:styled-content style="fixed-case">RCT</jats:styled-content>s) or placebo (<jats:styled-content style="fixed-case">RR</jats:styled-content> 1.48, 95% <jats:styled-content style="fixed-case">CI</jats:styled-content> 0.15–14.84, <jats:italic>I</jats:italic><jats:sup>2</jats:sup> = 21%; 2 <jats:styled-content style="fixed-case">RCT</jats:styled-content>s).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Despite previous evidence supporting the association of non‐vitamin K antagonist oral anticoagulants and overall <jats:styled-content style="fixed-case">GI</jats:styled-content> bleeding, non‐vitamin K antagonist oral anticoagulants are not associated with increased risk of major <jats:styled-content style="fixed-case">GI</jats:styled-content> bleeding compared to other anticoagulant drugs (with known increased risk of these events).</jats:p></jats:sec>

• 出版日期2015-12