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Гастроинтестинальные осложнения у пациентов, получающих антитромботическую и антикоагулянтную терапию
Ливзан М.А., Ширинская Н.В. Гастроинтестинальные осложнения у пациентов, получающих антитромботическую и антикоагулянтную терапию. Consilium Medicum. 2019; 21 (8): 71–73. DOI: 10.26442/20751753.2019.8.190531
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Livzan M.A., Shirinskaya N.V. Gastrointestinal complications in patients receiving antiplatelet and anticoagulant therapy. Consilium Medicum. 2019; 21 (8): 71–73. DOI: 10.26442/20751753.2019.8.190531
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Аннотация
Гастроинтестинальные осложнения лекарственной терапии остаются актуальными в практике внутренних болезней в течение нескольких десятилетий. Если раньше в качестве основных неблагоприятных агентов чаще всего упоминались нестероидные противовоспалительные препараты, то в последние годы в связи с изменением «портрета» коморбидного пациента на первые позиции выступают антикоагулянты и антиагреганты. Это связано с увеличением продолжительности жизни, а также внедрением в повседневную практику интервенционных методов лечения пациентов. В настоящий момент антитромбоцитарная и антикоагулянтная терапия широко используется у лиц с кардиологической патологией. В то же время гастроинтестинальные кровотечения являются одними из самых серьезных осложнений такой терапии. В статье обобщены данные по механизмам риска развития гастроинтестинальных осложнений (кровотечений, эрозивно-язвенных изменений верхних отделов пищеварительного тракта) у лиц, принимающих антиагреганты и антикоагулянты. Приведены данные, указывающие на ряд особенностей возникновения таких изменений при приеме отдельных групп антикоагулянтной и антитромбоцитарной терапии. Сделан акцент о необходимости выработки клинических рекомендаций для реальной клинической практики с учетом стратификации всех рисков, как кардиальных, ишемических, так и гастроинтестинальных.
Ключевые слова: гастроинтестинальные осложнения, гастроинтестинальные кровотечения, антитромботическая терапия, антикоагулянтная терапия.
Ключевые слова: гастроинтестинальные осложнения, гастроинтестинальные кровотечения, антитромботическая терапия, антикоагулянтная терапия.
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Gastrointestinal complications of medicinal therapy remain relevant in practice of internal diseases within several decades. If earlier, drug, then the last years were most often mentioned as the main adverse agents Nonsteroidal anti-inflammatory drugs, in connection with change of a portrait of the comorbid patient on the first positions anticoagulant and antiagregant tratment. It is connected with increase in life expectancy and also introduction in daily practice of intervention methods of treatment of patients. At present moment antithrombotic and anticoagulant therapy is widely used at patients with cardiological pathology. At the same time gastrointestinal bleedings are one of the most serious complications of such therapy. In article data on mechanisms of risk of development the gastrointestinal bleedings at the persons accepting antiagregant and anticoagulants treatment are generalized.The data indicating a number of features of emergence of such changes at reception of separate groups of anticoagulant and antiagregant tretment are provided. The emphasis about need of development of clinical recommendations for real clinical practice taking into account stratification of all risks as cardial, ischemic, and gastrointestinal is placed.
Key words: gastrointestinal complications, gastrointestinal bleeding, antithrombotic therapy, anticoagulant therapy.
Key words: gastrointestinal complications, gastrointestinal bleeding, antithrombotic therapy, anticoagulant therapy.
Полный текст
Список литературы
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2. Щербо А.П., Ширинская Н.В. Проблемы индикативного сопровождения пациентов с коморбидностью. Клин. геронтология. 2017; 23 (5–6): 64–8.
[Shcherbo A.P., Shirinskaia N.V. Problemy indikativnogo soprovozhdeniia patsientov s komorbidnost'iu. Klin. gerontologiia. 2017; 23 (5–6): 64–8 (in Russian).]
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[Livzan M.A., Kostenko M.B. Iazvennaia bolezn': sovremennye podkhody k diagnostike i terapii. Lechashchii vrach. 2010; 7 (20) (in Russian).]
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10. Yeomans ND, Lanas AI, Talley NJ et al. Prevalence and incidence of gastroduodenal ulcers during treatment with vascular protective doses of aspirin. Aliment Pharmacol Ther 2005; 22: 795–801.
11. McQuaid KR, Laine L. Systematic review and meta-analysis of adverse events of low-dose aspirin and clopidogrel in randomized controlled trials. Am J Med 2006; 119: 624–38.
12. Li L, Geraghty OC, Mehta Z et al. Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular events: a population-based cohort study. Lancet 2017; 390 (10093): 490–9.
13. Yusuf S, Zhao F, Mehta SR et al. Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345: 494–502.
14. Wiviott SD, Braunwald E, McCabe CH et al; TRITONTIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357: 2001–15.
15. Wallentin L, Becker RC, Budaj A et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361: 1045–57.
16. De Lemos JA, Brilakis ES. No free lunches: balancing bleeding and efficacy with ticagrelor. Eur Heart J 2011; 32: 2919–21.
17. Xu W-W, Hu S-J, Wu T. Risk analysis of new oral anticoagulants for gastrointestinal bleeding and intracranial hemorrhage in atrial fibrillation patients: a systematic review and network meta-analysis. J Zhejiang University-Science B 2017; 18 (7): 567–76.
18. Lanas A, García-Rodríguez LA, Arroyo MT et al. Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo-oxygenase-2 inhibitors, traditional non-aspirin nonsteroidal anti-inflammatory drugs, aspirin and combinations. Gut 2006; 55: 1731–8.
19. Desai J, Kolb JM, Weitz JI, Aisenberg J. Gastrointestinal bleeding with the new oral anticoagulants--defining the issues and the management strategies. Thromb Haemost 2013; 110: 205–12.
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22. 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; 123: 2363–72.
23. Blech S, Ebner T, Ludwig-Schwellinger E et al. The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans. Drug Metab Dispos 2008; 36: 386–99.
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25. Diener HC, Aisenberg J, Ansell J et al. Choosing a particular oral anticoagulant and dose for stroke prevention in individual patients with non-valvular atrial fibrillation: part 2. Eur Heart J 2017; 38 (12): 860–8.
26. Graham DJ, Reichman ME, Wernecke M et al. Stroke, Bleeding, and Mortality Risks in Elderly Medicare Beneficiaries Treated With Dabigatran or Rivaroxaban for Nonvalvular Atrial Fibrillation. JAMA Intern Med 2016; 176: 1662–71.
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28. Connolly SJ, Ezekowitz MD, Yusuf S et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139–51.
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30. Granger CB, Alexander JH, McMurray JJ et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365: 981–92.
31. Giugliano RP, Ruff CT, Braunwald E et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013; 369: 2093–104.
32. Hsu PI, Tsai TJ. Epidemiology of upper gastrointestinal damage associated with low-dose aspirin. Curr Pharm Des 2015; 21 (35): 5049–55.
33. Cheung KS, Leung WK. Gastrointestinal bleeding in patients on novel oral аnticoagulants: risk, prevention and management. World J Gastroenterol 2017; 23 (11): 1954–63.
34. Izumikawa K, Inaba T, Mizukawa S et al. Two cases of dabigatran-induced esophageal ulcer indicating the usefulness of drug administration guidance. Nihon Shokakibyo Gakkai Zasshi 2014; 111 (6): 1096–104.
35. Scheppach W, Meesmann M. Exfoliative esophagitis while taking dabigatran. Dtsch Med Wochenschr 2015; 140 (7): 515–8.
36. Карпов Ю.А. Исследование безопасности и эффективности апиксабана у пациентов с неклапанной фибрилляцией предсердий в реальной клинической практике в России. Атмосфера. Новости кардиологии. 2018; 4 (4): 3–12.
[Karpov Iu.A. Issledovanie bezopasnosti i effektivnosti apiksabana u patsientov s neklapannoi fibrilliatsiei predserdii v real'noi klinicheskoi praktike v Rossii. Atmosfera. Novosti kardiologii. 2018; 4 (4): 3–12 (in Russian).]
37. Комаров А.Л., Новикова Е.С., Добровольский А.Б. и др. Прогностическое значение оценки по шкале DAPT и уровня В-димера у больных, подвергаемых плановым чрескожным коронарным вмешательствам. Кардиолог. вестн. 2018; 13 (2): 39–47.
[Komarov A.L., Novikova E.S., Dobrovol'skii A.B. i dr. Prognosticheskoe znachenie otsenki po shkale DAPT i urovnia V-dimera u bol'nykh, podvergaemykh planovym chreskozhnym koronarnym vmeshatel'stvam. Kardiolog. vestn. 2018; 13 (2): 39–47 (in Russian).]
38. Мороз Е.В., Артемкин Э.Н., Крюков Е.В., Чернецов В.А. Осложнения со стороны желудочно-кишечного тракта при антитромботической терапии. Общая реаниматология. 2018; 14 (3): 15–26.
[Moroz E.V., Artemkin E.N., Kriukov E.V., Chernetsov V.A. Oslozhneniia so storony zheludochno-kishechnogo trakta pri antitromboticheskoi terapii. Obshchaia reanimatologiia. 2018; 14 (3): 15–26 (in Russian).]
39. Lip GY, Andreotti F, Fauchier L et al. Bleeding risk assessment and management in atrial fibrillation patients. Executive Summary of a Position Document from the European Heart Rhythm Association [EHRA], endorsed by the European Society of Cardiology [ESC] Working Group on Thrombosis. Thromb Haemost 2011; 106: 997–1011.
40. Sousa-Uva M, Neumann FJ, Ahlsson A et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur J Cardiothorac Surg 2019; 55 (1): 4–90.
2. Щербо А.П., Ширинская Н.В. Проблемы индикативного сопровождения пациентов с коморбидностью. Клин. геронтология. 2017; 23 (5–6): 64–8.
[Shcherbo A.P., Shirinskaia N.V. Problemy indikativnogo soprovozhdeniia patsientov s komorbidnost'iu. Klin. gerontologiia. 2017; 23 (5–6): 64–8 (in Russian).]
3. Ливзан М.А., Костенко М.Б. Язвенная болезнь: современные подходы к диагностике и терапии. Лечащий врач. 2010; 7 (20).
[Livzan M.A., Kostenko M.B. Iazvennaia bolezn': sovremennye podkhody k diagnostike i terapii. Lechashchii vrach. 2010; 7 (20) (in Russian).]
4. You JJ, Singer DE, Howard PA et al. Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: e531S–575S.
5. Lanas-Gimeno A, Lanas A. Risk of gastrointestinal bleeding during anticoagulant treatment. Exp Opin Drug Saf 2017; 16 (6): 673–85.
6. Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidalantiinflammatory drugs. N Engl J Med 1999; 340: 1888–99.
7. Lichtenberger LM, Richards JE, Hills BA. Effect of 16,16-dimethyl prostaglandin E2on the surface hydrophobicity of aspirin-treated canine gastric mucosa. Gastroenterology 1985; 88: 308–14.
8. Scheiman JM. NSAIDs, gastrointestinal injury, and cytoprotection. Gastroenterol Clin North Am 1996; 25: 279–98.
9. Antithrombotic Trialists’ Collaboration. Collaborative metaanalysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002; 324: 71–86.
10. Yeomans ND, Lanas AI, Talley NJ et al. Prevalence and incidence of gastroduodenal ulcers during treatment with vascular protective doses of aspirin. Aliment Pharmacol Ther 2005; 22: 795–801.
11. McQuaid KR, Laine L. Systematic review and meta-analysis of adverse events of low-dose aspirin and clopidogrel in randomized controlled trials. Am J Med 2006; 119: 624–38.
12. Li L, Geraghty OC, Mehta Z et al. Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular events: a population-based cohort study. Lancet 2017; 390 (10093): 490–9.
13. Yusuf S, Zhao F, Mehta SR et al. Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345: 494–502.
14. Wiviott SD, Braunwald E, McCabe CH et al; TRITONTIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357: 2001–15.
15. Wallentin L, Becker RC, Budaj A et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361: 1045–57.
16. De Lemos JA, Brilakis ES. No free lunches: balancing bleeding and efficacy with ticagrelor. Eur Heart J 2011; 32: 2919–21.
17. Xu W-W, Hu S-J, Wu T. Risk analysis of new oral anticoagulants for gastrointestinal bleeding and intracranial hemorrhage in atrial fibrillation patients: a systematic review and network meta-analysis. J Zhejiang University-Science B 2017; 18 (7): 567–76.
18. Lanas A, García-Rodríguez LA, Arroyo MT et al. Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo-oxygenase-2 inhibitors, traditional non-aspirin nonsteroidal anti-inflammatory drugs, aspirin and combinations. Gut 2006; 55: 1731–8.
19. Desai J, Kolb JM, Weitz JI, Aisenberg J. Gastrointestinal bleeding with the new oral anticoagulants--defining the issues and the management strategies. Thromb Haemost 2013; 110: 205–12.
20. Desai J, Granger CB, Weitz JI, Aisenberg J. Novel oral anticoagulants in gastroenterology practice. Gastrointest Endosc 2013; 78: 227–39.
21. Lim YJ, Yang CH. Non-steroidal anti-inflammatory drug-induced enteropathy. Clin Endosc 2012; 45: 138–44.
22. 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; 123: 2363–72.
23. Blech S, Ebner T, Ludwig-Schwellinger E et al. The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans. Drug Metab Dispos 2008; 36: 386–99.
24. Piccini JP, Garg J, Patel MR et al. Management of major bleeding events in patients treated with rivaroxaban vs. warfarin: results from the ROCKET AF trial. Eur Heart J 2014; 35: 1873–80.
25. Diener HC, Aisenberg J, Ansell J et al. Choosing a particular oral anticoagulant and dose for stroke prevention in individual patients with non-valvular atrial fibrillation: part 2. Eur Heart J 2017; 38 (12): 860–8.
26. Graham DJ, Reichman ME, Wernecke M et al. Stroke, Bleeding, and Mortality Risks in Elderly Medicare Beneficiaries Treated With Dabigatran or Rivaroxaban for Nonvalvular Atrial Fibrillation. JAMA Intern Med 2016; 176: 1662–71.
27. Patel MR, Mahaffey KW, Garg J et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365: 883–91.
28. Connolly SJ, Ezekowitz MD, Yusuf S et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361: 1139–51.
29. Goudevenos J, Pipilis A, Vardas P. Novel oral anticoagulants in atrial fibrillation: will the benefit outweigh the cost? Hellenic J Cardiol 2012; 53: 137–41.
30. Granger CB, Alexander JH, McMurray JJ et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011; 365: 981–92.
31. Giugliano RP, Ruff CT, Braunwald E et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013; 369: 2093–104.
32. Hsu PI, Tsai TJ. Epidemiology of upper gastrointestinal damage associated with low-dose aspirin. Curr Pharm Des 2015; 21 (35): 5049–55.
33. Cheung KS, Leung WK. Gastrointestinal bleeding in patients on novel oral аnticoagulants: risk, prevention and management. World J Gastroenterol 2017; 23 (11): 1954–63.
34. Izumikawa K, Inaba T, Mizukawa S et al. Two cases of dabigatran-induced esophageal ulcer indicating the usefulness of drug administration guidance. Nihon Shokakibyo Gakkai Zasshi 2014; 111 (6): 1096–104.
35. Scheppach W, Meesmann M. Exfoliative esophagitis while taking dabigatran. Dtsch Med Wochenschr 2015; 140 (7): 515–8.
36. Карпов Ю.А. Исследование безопасности и эффективности апиксабана у пациентов с неклапанной фибрилляцией предсердий в реальной клинической практике в России. Атмосфера. Новости кардиологии. 2018; 4 (4): 3–12.
[Karpov Iu.A. Issledovanie bezopasnosti i effektivnosti apiksabana u patsientov s neklapannoi fibrilliatsiei predserdii v real'noi klinicheskoi praktike v Rossii. Atmosfera. Novosti kardiologii. 2018; 4 (4): 3–12 (in Russian).]
37. Комаров А.Л., Новикова Е.С., Добровольский А.Б. и др. Прогностическое значение оценки по шкале DAPT и уровня В-димера у больных, подвергаемых плановым чрескожным коронарным вмешательствам. Кардиолог. вестн. 2018; 13 (2): 39–47.
[Komarov A.L., Novikova E.S., Dobrovol'skii A.B. i dr. Prognosticheskoe znachenie otsenki po shkale DAPT i urovnia V-dimera u bol'nykh, podvergaemykh planovym chreskozhnym koronarnym vmeshatel'stvam. Kardiolog. vestn. 2018; 13 (2): 39–47 (in Russian).]
38. Мороз Е.В., Артемкин Э.Н., Крюков Е.В., Чернецов В.А. Осложнения со стороны желудочно-кишечного тракта при антитромботической терапии. Общая реаниматология. 2018; 14 (3): 15–26.
[Moroz E.V., Artemkin E.N., Kriukov E.V., Chernetsov V.A. Oslozhneniia so storony zheludochno-kishechnogo trakta pri antitromboticheskoi terapii. Obshchaia reanimatologiia. 2018; 14 (3): 15–26 (in Russian).]
39. Lip GY, Andreotti F, Fauchier L et al. Bleeding risk assessment and management in atrial fibrillation patients. Executive Summary of a Position Document from the European Heart Rhythm Association [EHRA], endorsed by the European Society of Cardiology [ESC] Working Group on Thrombosis. Thromb Haemost 2011; 106: 997–1011.
40. Sousa-Uva M, Neumann FJ, Ahlsson A et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur J Cardiothorac Surg 2019; 55 (1): 4–90.
________________________________________________
1. Klein A, Gralnek IM. Acute, nonvariceal upper gastrointestinal bleeding. Curr Opin Crit Care 2015; 21: 154–62.
2. Shcherbo A.P., Shirinskaia N.V. Problemy indikativnogo soprovozhdeniia patsientov s komorbidnost'iu. Klin. gerontologiia. 2017; 23 (5–6): 64–8 (in Russian).
3. Livzan M.A., Kostenko M.B. Iazvennaia bolezn': sovremennye podkhody k diagnostike i terapii. Lechashchii vrach. 2010; 7 (20) (in Russian).
4. You JJ, Singer DE, Howard PA et al. Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: e531S–575S.
5. Lanas-Gimeno A, Lanas A. Risk of gastrointestinal bleeding during anticoagulant treatment. Exp Opin Drug Saf 2017; 16 (6): 673–85.
6. Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidalantiinflammatory drugs. N Engl J Med 1999; 340: 1888–99.
7. Lichtenberger LM, Richards JE, Hills BA. Effect of 16,16-dimethyl prostaglandin E2on the surface hydrophobicity of aspirin-treated canine gastric mucosa. Gastroenterology 1985; 88: 308–14.
8. Scheiman JM. NSAIDs, gastrointestinal injury, and cytoprotection. Gastroenterol Clin North Am 1996; 25: 279–98.
9. Antithrombotic Trialists’ Collaboration. Collaborative metaanalysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002; 324: 71–86.
10. Yeomans ND, Lanas AI, Talley NJ et al. Prevalence and incidence of gastroduodenal ulcers during treatment with vascular protective doses of aspirin. Aliment Pharmacol Ther 2005; 22: 795–801.
11. McQuaid KR, Laine L. Systematic review and meta-analysis of adverse events of low-dose aspirin and clopidogrel in randomized controlled trials. Am J Med 2006; 119: 624–38.
12. Li L, Geraghty OC, Mehta Z et al. Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular events: a population-based cohort study. Lancet 2017; 390 (10093): 490–9.
13. Yusuf S, Zhao F, Mehta SR et al. Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345: 494–502.
14. Wiviott SD, Braunwald E, McCabe CH et al; TRITONTIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357: 2001–15.
15. Wallentin L, Becker RC, Budaj A et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361: 1045–57.
16. De Lemos JA, Brilakis ES. No free lunches: balancing bleeding and efficacy with ticagrelor. Eur Heart J 2011; 32: 2919–21.
17. Xu W-W, Hu S-J, Wu T. Risk analysis of new oral anticoagulants for gastrointestinal bleeding and intracranial hemorrhage in atrial fibrillation patients: a systematic review and network meta-analysis. J Zhejiang University-Science B 2017; 18 (7): 567–76.
18. Lanas A, García-Rodríguez LA, Arroyo MT et al. Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo-oxygenase-2 inhibitors, traditional non-aspirin nonsteroidal anti-inflammatory drugs, aspirin and combinations. Gut 2006; 55: 1731–8.
19. Desai J, Kolb JM, Weitz JI, Aisenberg J. Gastrointestinal bleeding with the new oral anticoagulants--defining the issues and the management strategies. Thromb Haemost 2013; 110: 205–12.
20. Desai J, Granger CB, Weitz JI, Aisenberg J. Novel oral anticoagulants in gastroenterology practice. Gastrointest Endosc 2013; 78: 227–39.
21. Lim YJ, Yang CH. Non-steroidal anti-inflammatory drug-induced enteropathy. Clin Endosc 2012; 45: 138–44.
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Авторы
М.А. Ливзан*1, Н.В. Ширинская2
1 ФГБОУ ВО «Омский государственный медицинский университет» Минздрава России, Омск, Россия;
2 БУЗОО «Медицинский информационно-аналитический центр», Омск, Россия
*mlivzan@yandex.ru
1 ФГБОУ ВО «Омский государственный медицинский университет» Минздрава России, Омск, Россия;
2 БУЗОО «Медицинский информационно-аналитический центр», Омск, Россия
*mlivzan@yandex.ru
________________________________________________
Maria A. Livzan*1, Natalia V. Shirinskaya2
1 Omsk State Medical University, Omsk, Russia;
2 Omsk State Medical Information-Analytical Centre, Omsk, Russia
*mlivzan@yandex.ru
1 Omsk State Medical University, Omsk, Russia;
2 Omsk State Medical Information-Analytical Centre, Omsk, Russia
*mlivzan@yandex.ru
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