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Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 21, 2017; 23(11): 1954-1963
Published online Mar 21, 2017. doi: 10.3748/wjg.v23.i11.1954
Gastrointestinal bleeding in patients on novel oral anticoagulants: Risk, prevention and management
Ka-Shing Cheung, Wai K Leung
Ka-Shing Cheung, Wai K Leung, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
Author contributions: All authors contributed equally to this paper with literature review and analysis, drafting and critical revision and editing, and approval of the final version of this article.
Supported by the Li Shu Fan Medical Foundation Professorship (to Leung WK).
Conflict-of-interest statement: WKL has received honorarium for attending advisory board meetings of Boehringer Ingelheim and Takeda.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Wai K Leung, MD, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China. waikleung@hku.hk
Telephone: +852-22553348 Fax: +852-28162863
Received: December 13, 2016
Peer-review started: December 14, 2016
First decision: December 28, 2016
Revised: January 18, 2017
Accepted: March 2, 2017
Article in press: March 2, 2017
Published online: March 21, 2017
Abstract

Novel oral anticoagulants (NOACs), which include direct thrombin inhibitor (dabigatran) and direct factor Xa inhibitors (rivaroxaban, apixaban and edoxaban), are gaining popularity in the prevention of embolic stroke in non-valvular atrial fibrillation as well as in the prevention and treatment of venous thromboembolism. However, similar to traditional anticoagulants, NOACs have the side effects of bleeding, including gastrointestinal bleeding (GIB). Results from both randomized clinical trials and observations studies suggest that high-dose dabigatran (150 mg b.i.d), rivaroxaban and high-dose edoxaban (60 mg daily) are associated with a higher risk of GIB compared with warfarin. Other risk factors of NOAC-related GIB include concomitant use of ulcerogenic agents, older age, renal impairment, Helicobacter pylori infection and a past history of GIB. Prevention of NOAC-related GIB includes proper patient selection, using a lower dose of certain NOACs and in patients with renal impairment, correction of modifiable risk factors, and prescription of gastroprotective agents. Overt GIB can be managed by withholding NOACs followed by delayed endoscopic treatment. In severe bleeding, additional measures include administration of activated charcoal, use of specific reversal agents such as idarucizumab for dabigatran and andexanent alfa for factor Xa inhibitors, and urgent endoscopic management.

Keywords: Warfarin, Endoscopy, Apixaban, Edoxaban, Gastrointestinal bleeding, Dabigatran, Rivaroxaban, Novel anticoagulants

Core tip: Although effective in the prevention and treatment of thromboembolism, novel oral anticoagulants (NOACs) are still associated with bleeding complications including gastrointestinal bleeding (GIB). Physicians should exercise caution in the prescription of these drugs with careful review of the indications and appropriate dosage, as well as balancing the risks and benefits. Nonetheless, patients perceived to have an increased risk of GIB should not be precluded from taking NOACs, if they are also at a high risk of stroke. Instead, physicians should recognize the risk factors associated with NOAC-related GIB in order to undertake preventive measures to reduce the risk of GIB.