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Erschienen in: Digestive Diseases and Sciences 7/2018

27.03.2018 | Original Article

Locations and Mucosal Lesions Responsible for Major Gastrointestinal Bleeding in Patients on Warfarin or Dabigatran

verfasst von: Jennifer M. Kolb, Kathryn Friedman Flack, Prapti Chatterjee-Murphy, Jay Desai, Lars C. Wallentin, Michael Ezekowitz, Stuart Connolly, Paul Reilly, Martina Brueckmann, John Ilgenfritz, James Aisenberg

Erschienen in: Digestive Diseases and Sciences | Ausgabe 7/2018

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Abstract

Background and Aim

Different oral anticoagulants may be associated with gastrointestinal bleeding (GIB) from different locations or mucosal lesions. We aimed to test this hypothesis.

Methods

Two blinded gastroenterologists independently analyzed source documents from the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial of dabigatran 150 mg BID (D150), dabigatran 110 mg BID (D110) versus warfarin in non-valvular atrial fibrillation (NVAF).

Results

Major GIB events (total n = 546) and life-threatening GIB events (n = 258) were more common with D150 versus warfarin (RR 1.57 [1.28–1.92] and RR 1.62 [1.20–2.18], respectively) and similar for D110 compared to warfarin (RR 1.11 [0.89–1.38] and RR 1.16 [0.84–1.61], respectively). Fatal bleeding was similarly rare across treatment groups. Lower GI major bleeding and life-threatening bleeding were more common with D150 compared to warfarin (RR 2.23 [1.47, 3.38] and RR 2.64 [1.36, 5.13], respectively) and with D110 compared to warfarin (RR 1.78 [1.16, 2.75] and RR 2.00 [1.00, 4.00], respectively). MGIB from colonic angiodysplasia was increased with dabigatran versus warfarin (P < 0.01 for both dose comparisons). Subacute and chronic MGIB events were more common with D150 than with warfarin (RR 1.72 [1.06, 2.78] and RR 1.66 [1.12, 2.45], respectively), as were hematochezia or melena (RR 1.67 [1.18, 2.36] and RR 1.72 [1.20, 2.47], respectively).

Conclusions

In a chronic NVAF population, D150 but not D110 is associated with increased major and life-threatening GI bleeding in comparison with warfarin. At both dabigatran doses, increased bleeding from the colorectum, in particular from angiodysplasia, is seen.
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Literatur
1.
Zurück zum Zitat Sherwood MW, Douketis JD, Patel MR, et al. Outcomes of temporary interruption of rivaroxaban compared with warfarin in patients with nonvalvular. Circulation. 2014;129:1850–1859.CrossRefPubMedPubMedCentral Sherwood MW, Douketis JD, Patel MR, et al. Outcomes of temporary interruption of rivaroxaban compared with warfarin in patients with nonvalvular. Circulation. 2014;129:1850–1859.CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Michaels LBR. Relapses of thromboembolic disease after discontinued anticoagulant therapy. A comparison of the incidence after abrupt and after gradual termination of treatment. Am J Cardiol. 1967;20:670–673.CrossRefPubMed Michaels LBR. Relapses of thromboembolic disease after discontinued anticoagulant therapy. A comparison of the incidence after abrupt and after gradual termination of treatment. Am J Cardiol. 1967;20:670–673.CrossRefPubMed
3.
Zurück zum Zitat Landefeld CS, Rosenblatt MW, Goldman L. Bleeding in outpatients treated with warfarin: relation to the prothrombin time and important remediable lesions. Am J Med. 1989;87:153–159.CrossRefPubMed Landefeld CS, Rosenblatt MW, Goldman L. Bleeding in outpatients treated with warfarin: relation to the prothrombin time and important remediable lesions. Am J Med. 1989;87:153–159.CrossRefPubMed
4.
Zurück zum Zitat Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;17:1139–1151.CrossRef Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;17:1139–1151.CrossRef
5.
Zurück zum Zitat Flack KF, Desai J, Kolb JM, et al. Major gastrointestinal bleeding often is caused by occult malignancy in patients receiving warfarin or dabigatran atrial fibrillation. Clin Gastroenterol Hepatol. 2017;15:682–690.CrossRefPubMed Flack KF, Desai J, Kolb JM, et al. Major gastrointestinal bleeding often is caused by occult malignancy in patients receiving warfarin or dabigatran atrial fibrillation. Clin Gastroenterol Hepatol. 2017;15:682–690.CrossRefPubMed
6.
Zurück zum Zitat Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005;3:692–694.CrossRefPubMed Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005;3:692–694.CrossRefPubMed
7.
Zurück zum Zitat Connolly SJ, Ezekowitz MD, Yusuf S, Reilly PA, Wallentin LC. Newly identified events in the RE-LY trial. N Engl J Med. 2010;363:1875–1876.CrossRefPubMed Connolly SJ, Ezekowitz MD, Yusuf S, Reilly PA, Wallentin LC. Newly identified events in the RE-LY trial. N Engl J Med. 2010;363:1875–1876.CrossRefPubMed
8.
Zurück zum Zitat Eikelboom JW, Wallentin L, Connolly SJ, et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation. 2011;31:2363–2372.CrossRef Eikelboom JW, Wallentin L, Connolly SJ, et al. Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial. Circulation. 2011;31:2363–2372.CrossRef
9.
Zurück zum Zitat Sherwood MW, Nessel CC, Hellkamp AS, et al. Gastrointestinal bleeding in patients with atrial fibrillation treated with rivaroxaban or warfarin: ROCKET AF Trial. J Am Coll Cardiol. 2015;66:2271–2281.CrossRefPubMed Sherwood MW, Nessel CC, Hellkamp AS, et al. Gastrointestinal bleeding in patients with atrial fibrillation treated with rivaroxaban or warfarin: ROCKET AF Trial. J Am Coll Cardiol. 2015;66:2271–2281.CrossRefPubMed
10.
Zurück zum Zitat Hylek EM, Held C, Alexander JH, et al. Major bleeding in patients with atrial fibrillation receiving apixaban or warfarin. J Am Coll Cardiol. 2014;63:2141–2147.CrossRefPubMed Hylek EM, Held C, Alexander JH, et al. Major bleeding in patients with atrial fibrillation receiving apixaban or warfarin. J Am Coll Cardiol. 2014;63:2141–2147.CrossRefPubMed
11.
Zurück zum Zitat Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369:2093–2104.CrossRefPubMed Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369:2093–2104.CrossRefPubMed
12.
Zurück zum Zitat Abraham NS, Singh S, Alexander GC, et al. Comparative risk of gastrointestinal bleeding with dabigatran, rivaroxaban, and warfarin: population based cohort study. BMJ. 2015 Jan [cited 2016 Apr 30];350:h1857. Abraham NS, Singh S, Alexander GC, et al. Comparative risk of gastrointestinal bleeding with dabigatran, rivaroxaban, and warfarin: population based cohort study. BMJ. 2015 Jan [cited 2016 Apr 30];350:h1857.
13.
Zurück zum Zitat Pollack CV, Gruenenfelder F, Eikelboom J, et al. Initial experience with idarucizumab in dabigatran-treated patients presenting with acute gastrointestinal hemorrhage: interim results from the RE-VERSE AD study. Ann Emerg Med. 2015;66:S2–S3. Pollack CV, Gruenenfelder F, Eikelboom J, et al. Initial experience with idarucizumab in dabigatran-treated patients presenting with acute gastrointestinal hemorrhage: interim results from the RE-VERSE AD study. Ann Emerg Med. 2015;66:S2–S3.
14.
Zurück zum Zitat Casado Arroyo R, Polo-Tomas M, Roncales MP, Scheiman J, Lanas A. Lower GI bleeding is more common than upper among patients on dual antiplatelet therapy: long-term follow-up of a cohort of patients commonly using PPI co-therapy. Heart. 2012;98:718–723.CrossRefPubMed Casado Arroyo R, Polo-Tomas M, Roncales MP, Scheiman J, Lanas A. Lower GI bleeding is more common than upper among patients on dual antiplatelet therapy: long-term follow-up of a cohort of patients commonly using PPI co-therapy. Heart. 2012;98:718–723.CrossRefPubMed
15.
Zurück zum Zitat Nagata N, Niikura R, Yamada A, et al. Acute middle gastrointestinal bleeding risk associated with NSAIDs, antithrombotic drugs, and PPIs: a multicenter case-control study. PLoS One. 2016;11:e0151332.CrossRefPubMedPubMedCentral Nagata N, Niikura R, Yamada A, et al. Acute middle gastrointestinal bleeding risk associated with NSAIDs, antithrombotic drugs, and PPIs: a multicenter case-control study. PLoS One. 2016;11:e0151332.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Lanas Á, Carrera-Lasfuentes P, Arguedas Y, et al. Risk of upper and lower gastrointestinal bleeding in patients taking nonsteroidal anti-inflammatory drugs, antiplatelet agents, or anticoagulants. Clin Gastroenterol Hepatol. 2015;13:e2.CrossRef Lanas Á, Carrera-Lasfuentes P, Arguedas Y, et al. Risk of upper and lower gastrointestinal bleeding in patients taking nonsteroidal anti-inflammatory drugs, antiplatelet agents, or anticoagulants. Clin Gastroenterol Hepatol. 2015;13:e2.CrossRef
17.
Zurück zum Zitat Hansen ML, Sorensen R, Clausen MT, et al. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med. 2010;170:1433–1441.CrossRefPubMed Hansen ML, Sorensen R, Clausen MT, et al. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med. 2010;170:1433–1441.CrossRefPubMed
18.
Zurück zum Zitat Chan EW, Lau WCY, Leung WK, et al. Prevention of dabigatran-related gastrointestinal bleeding with gastroprotective agents: a population-based study. Gastroenterology. 2015;149:e3.CrossRef Chan EW, Lau WCY, Leung WK, et al. Prevention of dabigatran-related gastrointestinal bleeding with gastroprotective agents: a population-based study. Gastroenterology. 2015;149:e3.CrossRef
19.
Zurück zum Zitat Abraham NS. Prevention of gastrointestinal bleeding in patients receiving direct oral anticoagulants. Am J Gastroenterol Suppl. 2016;3:2–12.CrossRef Abraham NS. Prevention of gastrointestinal bleeding in patients receiving direct oral anticoagulants. Am J Gastroenterol Suppl. 2016;3:2–12.CrossRef
20.
Zurück zum Zitat Blech S, Ebner T, Ludwig-Schwellinger E, Stangier J, Roth W. The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans. Drug Metab Dispos. 2008;36:386–399.CrossRefPubMed Blech S, Ebner T, Ludwig-Schwellinger E, Stangier J, Roth W. The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans. Drug Metab Dispos. 2008;36:386–399.CrossRefPubMed
21.
Zurück zum Zitat Lanas-Gimeno A, Lanas A. Expert opinion on drug safety risk of gastrointestinal bleeding during anticoagulant treatment. Exp Opin Drug Saf. 2017;16:673–685.CrossRef Lanas-Gimeno A, Lanas A. Expert opinion on drug safety risk of gastrointestinal bleeding during anticoagulant treatment. Exp Opin Drug Saf. 2017;16:673–685.CrossRef
22.
Zurück zum Zitat Gerson LB, Fidler JL, Cave DR, Leighton JA. ACG clinical guideline: diagnosis and management of small bowel bleeding. Am J Gastroenterol. 2015;110:1265–1287.CrossRefPubMed Gerson LB, Fidler JL, Cave DR, Leighton JA. ACG clinical guideline: diagnosis and management of small bowel bleeding. Am J Gastroenterol. 2015;110:1265–1287.CrossRefPubMed
23.
Zurück zum Zitat Manno M, Riccioni ME, Cannizzaro R, Andreoli A, Marmo R, Pennazio M. Diagnostic and therapeutic yield of single balloon enteroscopy in patients with suspected small-bowel disease: results of the Italian multicentre study. Dig Liver Dis. 2013;45:211–215.CrossRefPubMed Manno M, Riccioni ME, Cannizzaro R, Andreoli A, Marmo R, Pennazio M. Diagnostic and therapeutic yield of single balloon enteroscopy in patients with suspected small-bowel disease: results of the Italian multicentre study. Dig Liver Dis. 2013;45:211–215.CrossRefPubMed
24.
Zurück zum Zitat van Turenhout ST, Jacobs MA, van Weyenberg SJ, et al. Diagnostic yield of capsule endoscopy in a tertiary hospital in patients with obscure gastrointestinal bleeding. J Gastrointestin Liver Dis. 2010;19:141–145.PubMed van Turenhout ST, Jacobs MA, van Weyenberg SJ, et al. Diagnostic yield of capsule endoscopy in a tertiary hospital in patients with obscure gastrointestinal bleeding. J Gastrointestin Liver Dis. 2010;19:141–145.PubMed
25.
Zurück zum Zitat Van Weyenberg SJB, Van Turenhout ST, Jacobs MAJM, Bouma G, Mulder CJJ. Video capsule endoscopy for previous overt obscure gastrointestinal bleeding in patients using anti-thrombotic drugs. Dig Endosc. 2012;24:247–254.CrossRefPubMed Van Weyenberg SJB, Van Turenhout ST, Jacobs MAJM, Bouma G, Mulder CJJ. Video capsule endoscopy for previous overt obscure gastrointestinal bleeding in patients using anti-thrombotic drugs. Dig Endosc. 2012;24:247–254.CrossRefPubMed
26.
Zurück zum Zitat Boal Carvalho P, Rosa B, Moreira MJ, Cotter J. New evidence on the impact of antithrombotics in patients submitted to small bowel capsule endoscopy for the evaluation of obscure gastrointestinal bleeding. Gastroenterol Res Pract. 2014;2014:709217.CrossRefPubMedPubMedCentral Boal Carvalho P, Rosa B, Moreira MJ, Cotter J. New evidence on the impact of antithrombotics in patients submitted to small bowel capsule endoscopy for the evaluation of obscure gastrointestinal bleeding. Gastroenterol Res Pract. 2014;2014:709217.CrossRefPubMedPubMedCentral
Metadaten
Titel
Locations and Mucosal Lesions Responsible for Major Gastrointestinal Bleeding in Patients on Warfarin or Dabigatran
verfasst von
Jennifer M. Kolb
Kathryn Friedman Flack
Prapti Chatterjee-Murphy
Jay Desai
Lars C. Wallentin
Michael Ezekowitz
Stuart Connolly
Paul Reilly
Martina Brueckmann
John Ilgenfritz
James Aisenberg
Publikationsdatum
27.03.2018
Verlag
Springer US
Erschienen in
Digestive Diseases and Sciences / Ausgabe 7/2018
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-018-5007-6

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