Gastrointestinal Bleeding in Antithrombotic Therapy in Patients with Coronary Heart Disease: Risk Factors, Pathogenesis and Treatment
https://doi.org/10.22416/1382-4376-2020-30-3-14-23
Abstract
Aim. Description of risk factors, pathogenesis and treatment strategies of gastrointestinal bleeding (GIB) in the course of antithrombotic therapy in patients with coronary heart disease (CHD).
Key points. Risk factors of GIB during antithrombotic therapy in CHD patients include: GIB, gastric and/or duodenal ulcer in the history, reflux esophagitis, presence of H. pylori, inflammatory bowel disease, diverticula, haemorrhoids, angiodysplasia, gastrointestinal neoplasia, age above 65 years, concomitant treatment with non-steroidal anti-inflammatory drugs (NSAIDs), glomerular filtration rate <50 mL/min, high doses of direct oral anticoagulants (DOACs) ≥3 in HAS-BLED score. Pathogenesis of GIB in the course of antithrombotic therapy is associated with systemic hypocoagulation and local damaging effects of these drugs. Strategies of GIB treatment during DOAC therapy in patients with CHD are determined by severity of bleeding and threat to life. Aside to standard conservative measures, endoscopic or surgical haemostasis requires usage of antidotes to suppress effects of DOACs and other specific drugs in severe cases.
Conclusion. GIB associated with antithrombotic therapy in CHD patients poses a serious medical problem of growing importance with wider application of anticoagulant drugs. Antithrombotic therapy requires accurate decision making, risk assessment, careful monitoring of the patient’s condition and timely diagnosis of gastrointestinal disorders following good rationale in GIB prevention.
About the Authors
N. S. LapinaRussian Federation
Natalya S. Lapina — Cand. Sci. (Med.), Research Assistant, Department of Hospital Therapy and General Practice named after V.G. Vogralik
603950, Nizhny Novgorod, Minina i Pozharskogo square, 10/1.
A. A. Alekseeva
Russian Federation
Anastasia A. Alekseeva — Graduate Student (5th year), Faculty of Medicine
603950, Nizhny Novgorod, Minina i Pozharskogo square, 10/1.
A. D. Vershinina
Russian Federation
Anna D. Vershinina — Graduate Student (5th year), Faculty of Medicine
603950, Nizhny Novgorod, Minina i Pozharskogo square, 10/1.
N. S. Khruleva
Russian Federation
Natalia S. Khruleva — Cand. Sci. (Med.), Research Assistant, Department of Hospital Therapy and General Practice named after V.G. Vogralik
603950, Nizhny Novgorod, Minina i Pozharskogo square, 10/1.
F. N. Muradova
Russian Federation
Fazile N. Muradova — Graduate Student (5th year), Faculty of Medicine
603950, Nizhny Novgorod, Minina i Pozharskogo square, 10/1.
L. Y. Koroleva
Russian Federation
Lyubov Y. Koroleva — Dr. Sci. (Med.), Prof., Department of Hospital Therapy and General Practice named after V.G. Vogralik
603950, Nizhny Novgorod, Minina i Pozharskogo square, 10/1.
References
1. Moroz E.V., Artemkin E.N., Kryukov E.V., Chernetsov V.A. Gastrointestinal complications in antithrombotic therapy. General Reanimatology. 2018;14(3):15–26 (In Russ.) DOI: 10.15360/1813-9779-2018-3-15-26
2. Valgimigli M., Bueno H., Byrne R.A., Collet J.P., Costa F., Jeppsson A., et al.; ESC Scientific Document Group. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. Eur J Cardiothorac Surg. 2018;53(1):34–78. DOI: 10.1093/ejcts/ezx334
3. Mehta S.R., Bainey K.R., Cantor W.J., Lordkipanidzé M., Marquis-Gravel G., Robinson S.D., et al; members of the Secondary Panel. 2018 Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology Focused Update of the Guidelines for the Use of Antiplatelet Therapy. Can J Cardiol. 2018;34(3):214–33. DOI: 10.1016/j.cjca.2017.12.012
4. Siller-Matula J., Huber K., Christ G., Schror K., Kubica J., Herkner H., et al. Impact of clopidogrel loading dose on clinical outcome in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis. Heart. 2011;97(2):98–105. DOI: 10.1136/hrt.2010.195438
5. Eikelboom J.W., Wallentin L., Connolly S.J., Ezekowitz M., Healey J.S., Oldgren J., 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(21):2363–72. DOI: 10.1161/CIRCULATIONAHA.110.004747
6. Schulman S., Kearon C., Kakkar A.K., Mismetti P., Schellong S., Eriksson H., et al. RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361(24):2342–52. DOI: 10.1056/NEJMoa0906598
7. Patel M.R., Mahaffey K.W., Garg J., Pan G., Singer D.E., Hacke W., et al. ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883–91. DOI: 10.1056/NEJMoa1009638
8. Giugliano R.P., Ruff C.T., Braunwald E., Murphy S.A., Wiviott S.D., Halperin J.L., et al. ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369(22):2093–104. DOI: 10.1056/NEJMoa1310907
9. Granger C.B., Alexander J.H., McMurray J.J., Lopes R.D., Hylek E.M., Hanna M., et al. ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–92. DOI: 10.1056/NEJMoa1107039
10. Miller C.S., Dorreen A., Martel M., Huynh T., Barkun A.N. Risk of Gastrointestinal Bleeding in Patients Taking Non-Vitamin K Antagonist Oral Anticoagulants: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 2017;15(11):1674–83. DOI: 10.1016/j.cgh.2017.04.031
11. Cardiovascular prevention 2017. National guidelines. Russ J Cardiol. 2018;23(6):7–122 (In Russ.) DOI: 10.15829/1560-4071-2018-6-7-122
12. GUSTO Investigators. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. NEJM. 1993;329(10):673–82. DOI: 10.1056/NEJM199309023291001
13. Rao S.V., Pratt C., Berke A., Jaffe A., Ockene I., Schreiber T.L., et al. ThromboLysis in MyocardiaL Infarction (TIMI) TriaL phase-I: hemorrhagic manifestations and changes in pLasma fibrino-gen system and fibrinoLytic system in patients treated with recombinant tissue pLasminogen activator and streptokinase. JACC. 1988;11(1):1–11. DOI: 10.21518/2079-701X-2017-12-138-143
14. Serebruany V.L., Atar D. Assessment of bleeding events in clinical trials — proposal of a new classification. Am J Cardiol. 2007;99(2):288–90. Erratum in: Am J Cardiol. 2007;100(3):562. PMID: 17223436
15. Pisters R., Lane D.A., Nieuwlaat R., de Vos C.B., Crijns H.J., Lip G.Y. A novel user-friendly score (HASBLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138(5):1093–100. DOI: 10.1378/chest.10-0134
16. Vicente V., Martín A., Lecumberri R., Coll-Vinent B., Suero C., González-Porras J.R., et al. Grupo DECOVER. Clinical perspectives on the management of bleeding in patients on oral anticoagulants: the DECOVER Study (DElphi Consensus on oral COagulation and therapy action reVERsal). Emergencias. 2017;29(1):18–26.
17. Lanas-Gimeno A., Lanas A. Risk of gastrointestinal bleeding during anticoagulant treatment. Expert Opin Drug Saf. 2017;16(6):673–85. DOI: 10.1080/14740338.2017.1325870
18. Albaladejo P., Samama C.M., Sié P., Kauffmann S., Mémier V., Suchon P., et al. GIHP-NACO Study Group. Management of Severe Bleeding in Patients Treated with Direct Oral Anticoagulants: An Observational Registry Analysis. Anesthesiology. 2017;127(1):111–20. DOI: 10.1097/ALN.0000000000001631
19. Lauffenburger J.C., Rhoney D.H., Farley J.F., Gehi A.K., Fang G. Predictors of gastrointestinal bleeding among patients with atrial fibrillation after initiating dabigatran therapy. Pharmacotherapy. 2015;35(6):560–8. DOI: 10.1002/phar.1597
20. Ivashkin V.T., Sheptulin A.A., Mayev I.V., Baranskaya Ye.K., Trukhmanov A.S., Lapina T.L. Russian gastroenterological association clinical guidelines on diagnostics and treatment of NSAIDsassociated erosive and ulcerative lesions of the stomach and duodenum. Rus J Gastroenterol Hepatol Coloproctol. 2014;25(6):89–94 (In Russ.)
21. Malfertheiner P., Megraud F., O’Morain C.A, Gisbert J.P., Kuipers E.J., Axon A.T., et al. European Helicobacter and Microbiota Study Group and Consensus panel. Management of Helicobacter pylori infectionthe Maastricht V/Florence Consensus Report. Gut. 2017;66(1):6–30. DOI: 10.1136/gutjnl-2016-312288
22. Karateev A.E., Nasonov E.L., Yakhno N.N., Ivashkin V.T., Chichasova N.V., Alekseeva L.I., et al. Clinical guidelines «Rational use of non-steroidal anti-inflammatory drugs (NSAIDs) in clinical practice». Current Rheumatology. 2015;9(1):4–23 (In Russ.) DOI: 10.14412/1996-7012-2015-1-4-23
23. Cryer B., Feldman M. Effects of very low dose daily, long-term aspirin therapy on gastric, duodenal, and rectal prostaglandin levels and on mucosal injury in healthy humans. Gastroenterology. 1999;117(1):17–25.
24. Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002;324(7329):71–86. Erratum in: BMJ 2002;324(7330):141.
25. Cooke A.R., Hunt J.N. Absorption of acetylsalicylic acid from unbuffered and buffered gastric contents. Am J Dig Dis. 1970;15(2):95–102. PMID: 4905590
26. Graham D.Y., Smith J.L. Aspirin and the Stomach. Ann Intern Med. 1986;104:390–8. DOI: 10.7326/0003-4819-104-3-390
27. Fork F.T., Lafolie P., Tóth E., Lindgärde F. Gastroduodenal tolerance of 75 mg clopidogrel versus 325 mg aspirin in healthy volunteers. A gastroscopic study. Scand J Gastroenterol. 2000;35(5):464–9.
28. Kirichenko A.A., Ebzeeva E.Yu. Acetylsalicylic acid in secondary prevention of cardiovascular complications. Consilium Medicum. 2019;21(5):28–31 (In Russ.) DOI: 10.26442/20751753.2019.5.190454
29. Leung W.K., Bjarnason I., Wong V.W., Sung J.J., Chan F.K. Small bowel enteropathy associated with chronic low-dose aspirin therapy. Lancet. 2007;369(9561):614.
30. Endo H., Sakai E., Kato T., Umezawa S., Higurashi T., Ohkubo H., Nakajima A. Small bowel injury in low-dose aspirin users. J Gastroenterol. 2015;50(4):378–86. DOI: 10.1007/s00535-014-1028-x
31. Watanabe T., Sugimori S., Kameda N., Machida H., Okazaki H., Tanigawa T., et al. Small bowel injury by low-dose enteric-coated aspirin and treatment with misoprostol: a pilot study. Clin Gastroenterol Hepatol. 2008;6(11):1279–82. DOI: 10.1016/j.cgh.2008.06.021
32. Smecuol E., Sanchez M., Suarez A., Argonz J.E., Sugai E., Vazquez H., et al. Low-dose aspirin affects the small bowel mucosa: results of a pilot study with a multidimensional assessment. Clin Gastroenterol Hepatol. 2009;7(5):524–9. DOI: 10.1016/j.cgh.2008.12.019; 134-141
33. Utzeri E., Usai P. Role of non-steroidal anti-inflammatory drugs on intestinal permeability and nonalcoholic fatty liver disease. World J Gastroenterol. 2017;23(22):3954–63. DOI: 10.3748/wjg.v23.i22.3954
34. Wallace J.L., Syer S., Denou E., de Palma G., Vong L., McKnight W., et al. Proton pump inhibitors exacerbate NSAID-induced small intestinal injury by inducing dysbiosis. Gastroenterology. 2011;141(4):1314–22, 1322.e1–5. DOI: 10.1053/j.gastro.2011.06.075
35. Endo H., Sakai E., Taniguchi L., Kessoku T., Komiya Y., Ezuka A., et al. Risk factors for small-bowel mucosal breaks in chronic low-dose aspirin users: data from a prospective multicenter capsule endoscopy registry. Gastrointest Endosc. 2014;80(5):826–34. DOI: 10.1016/j.gie.2014.03.024
36. Iwamoto J., Mizokami Y., Saito Y., Shimokobe K., Honda A., Ikegami T., et al. Small-bowel mucosal injuries in low-dose aspirin users with obscure gastrointestinal bleeding. World J Gastroenterol. 2014;20(36):13133–8. DOI: 10.3748/wjg.v20.i36.13133
37. Karateev A.E., Moroz E.V., Kryukov E.V. Small intestinal damage associated with the use of nonsteroidal anti-inflammatory drugs. Almanac of Clinical Medicine. 2019;47(6):559–67 (In Russ.) DOI: 10.18786/2072-0505-2019-47-048
38. Bjarnason I., Scarpignato C., Holmgren E., Olszewski M., Rainsford K.D., Lanas A. Mechanisms of Damage to the Gastrointestinal Tract From Nonsteroidal Anti-Inflammatory Drugs. Gastroenterology. 2018;154(3):500–14. DOI: 10.1053/j.gastro.2017.10.049
39. Karateev A.E., Nasonov E.L., Ivashkin V.T., Martynov A.I., Yakhno N.N., Arutyunov G.P., et al. Rational use of nonsteroidal anti-inflammatory drugs. Clinical guidelines. Rheumatology Science and Practice. 2018;56:1–29 (In Russ.) DOI: 10.14412/1995-4484-2018-1-29
40. Bhatt D.L., Scheiman J., Abraham N.S., Antman E.M., Chan F.K., Furberg C.D., et al. American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. Circulation. 2008;118(18):1894–909. DOI: 10.1161/CIRCULATIONAHA.108.191087
41. Wallentin L., Becker R.C., Budaj A., Cannon C.P., Emanuelsson H., Held C., Horrow J., Husted S., James S., Katus H., Mahaffey K.W., Scirica B.M., Skene A., Steg P.G., Storey R.F., Harrington R.A.; PLATO Investigators, Freij A, Thorsén M. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045–57. DOI: 10.1056/NEJMoa0904327
42. Montalescot G., Wiviott S.D., Braunwald E., Murphy S.A., Gibson C.M., McCabe C.H., et al. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet. 2009;373(9665):723–31. DOI: 10.1016/S0140-6736(09)60441-4
43. Cheung K.S., Leung W.K. Gastrointestinal bleeding in patients on novel oral anticoagulants: Risk, prevention and management. World J Gastroenterol. 2017;23(11):1954–63. DOI: 10.3748/wjg.v23.i11.1954
44. Desai J., Kolb J.M., Weitz J.I., Aisenberg J. Gastrointestinal bleeding with the new oral anticoagulants — defining the issues and the management strategies. Thromb Haemost. 2013;110(2):205–12. DOI: 10.1160/TH13-02-0150
45. Kundu A., Sardar P., Sen P., Chatterjee S., Huston J., Nairooz R., et al. Patient Taking A Novel Oral Anticoagulant Presents With Major GI Bleeding. J Atr Fibrillation. 2015;8(3):1218. DOI: 10.4022/jafib.1218
46. Desai J., Granger C.B., Weitz J.I., Aisenberg J. Novel oral anticoagulants in gastroenterology practice. Gastrointest Endosc. 2013;78(2):227–39. DOI: 10.1016/j.gie.2013.04.179
47. 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(2):386–99.
48. Toya Y., Nakamura S., Tomita K., Matsuda N., Abe K., Abiko Y., et al. Dabigatran-induced esophagitis: The prevalence and endoscopic characteristics. J Gastroenterol Hepatol. 2016;31(3):610–4. DOI: 10.1111/jgh.13024
49. Thomopoulos K.C., Mimidis K.P., Theocharis G.J., Gatopoulou A.G., Kartalis G.N., Nikolopoulou V.N. Acute upper gastrointestinal bleeding in patients on long-term oral anticoagulation therapy: endoscopic findings, clinical management and outcome. World J Gastroenterol. 2005;11(9):1365–8.
50. Rubin T.A., Murdoch M., Nelson D.B. Acute GI bleeding in the setting of supratherapeutic international normalized ratio in patients taking warfarin: endoscopic diagnosis, clinical management, and outcomes. Gastrointest Endosc. 2003;58(3):369–73.
51. Endo H., Hosono K., Inamori M., Nozaki Y., Yoneda K., Fujita K., et al. Characteristics of small bowel injury in symptomatic chronic low-dose aspirin users: the experience of two medical centers in capsule endoscopy. J Gastroenterol. 2009;44(6):544–9. DOI: 10.1007/s00535-009-0040-z
52. Balabantseva A.P., Karateev A.E. Frequency and clinical endoscopic features of combined NSAID-induced gastrointestinal lesions. Current Rheumatology. 2018;12(4):95–100 (In Russ.) DOI: 10.14412/1996-7012-2018-4-95-100.
53. Vakhrushev N.M., Zagrebina E.A. Enteropathy induced by non-steroidal anti-inflammatory drugs (pathogenesis, diagnosis, treatment). Therapeutic Archive. 2012;(5):74–9 (In Russ.) ISSN: 2309-5342
54. Rao S.V., Eikelboom J., Steg P.G., Lincoff A.M., Weintraub W.S., Bassand J.P., et al., Academic Bleeding Consensus Multidisciplinary Working Group. Standardized reporting of bleeding complications for clinical investigations in acute coronary syndromes: a proposal from the academic bleeding consensus (ABC) multidisciplinary working group. Am Heart J. 2009;158(6):881–6.e1. DOI: 10.1016/j.ahj.2009.10.008
55. Flack K.F., Desai J., Kolb J.M., Chatterjee P., Wallentin L.C., Ezekowitz M., et al. Major Gastrointestinal Bleeding Often Is Caused by Occult Malignancy in Patients Receiving Warfarin or Dabigatran to Prevent Stroke and Systemic Embolism From Atrial Fibrillation. Clin Gastroenterol Hepatol. 2017;15(5):682–90. DOI: 10.1016/j.cgh.2016.10.011
56. Sostres C., Gargallo C.J., Arroyo M.T., Lanas A. Adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs, aspirin and coxibs) on upper gastrointestinal tract. Best Pract Res Clin Gastroenterol. 2010;24(2):121–32. DOI: 10.1016/j.bpg.2009.11.005
57. Baranovskiy A.Yu. Diagnosis, prevention and treatment of NSAID-induced colonopathy. Experimental and Clinical Gastroenterology. 2017:146(10);4–14 (In Russ.) DOI: 10.31146/1682-8658-ecg
58. Goldstein J.L., Eisen G.M., Lewis B., Gralnek I.M., Zlotnick S., Fort J.G. on behalf of the investigators. Video capsule endoscopy to prospectively assess small bowel injury with celecoxib, naproxen plus omeprazole, and placebo. Clin Gastroenterol Hepatol. 2005;3(2):133–41. DOI: 10.1016/S1542-3565(04)00619-6.16
59. Tai F.W.D., McAlindon M.E. NSAIDs and the small bowel. Curr Opin Gastroenterol. 2018;34(3):175–82. DOI: 10.1097/MOG.0000000000000427
60. Sands G., Shell B., Zhang R. Adverse events in patients with blood loss: a pooled analysis of 51 clinical studies from the celecoxib clinical trial database. Open Rheumatol J. 2012;6:44–9. DOI: 10.2174/1874312901206010044
61. Kanorskiy S.G., Gilyarevskiy S.R., Tarasov A.V., Zhuk V.S., Yavelov I.S. New New EHRA recommendations on anticoagulant therapy in patients with atrial fibrillation: comments of Russian experts. International Journal of Heart and Vascular Diseases. DOI: 10.15829/2311-1623-6-19
62. Maev I.V., Kucheryavyi Yu.A., Oganesyan T.S. Diagnosis and treatment of nonvariceal upper gastrointestinal bleeding: a general practitioner’s view. Farmateka.2011;2:32–9 (In Russ.) ISSN: 2414–9128
63. Steffel J., Verhamme P., Potpara T., Albaladejo P., Antz M., Desteghe L., et al. The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. European Heart Journal. 2018;39(16):1330–93. DOI: 10.1093/eurheartj/ehy136
64. Radaelli F., Dentali F., Repici A., Amato A., Paggi S., Rondonotti E., Dumonceau J.M. Management of anticoagulation in patients with acute gastrointestinal bleeding. Dig Liver Dis. 2015;47(8):621–7. DOI: 10.1016/j.dld.2015.03.029
65. Biecker E. Diagnosis and therapy of non-variceal upper gastrointestinal bleeding. World J Gastrointest Pharmacol Ther. 2015;6(4):172–82. DOI: 10.4292/wjgpt.v6.i4.172
66. Green F.W. Jr., Kaplan M.M., Curtis L.E., Levine P.H. Effect of acid and pepsin on blood coagulation and platelet aggregation. A possible contributor prolonged gastroduodenal mucosal hemorrhage. Gastroenterology. 1978;74(1):38–43.
67. Maev I.V., Goncharenko A.Yu., Dicheva D.T., Andreyev D.N., Shvydko V.S., Buragina T.A. Peptic ulcer bleeding treatment and recurrence prevention: a general practitioner’s view. Medical Council.l. 2013;(10):22–6 (In Russ.) DOI: 10.21518/2079-701X-2013-10-22-26
68. Barkun A.N., Bardou M., Kuipers E.J., Sung J., Hunt R.H., Martel M., Sinclair P., International Consensus Upper Gastrointestinal Bleeding Conference Group. International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med. 2010;152(2):101–13. DOI: 10.7326/0003-4819-152-2-201001190-00009
69. Barkun A.N., Almadi M., Kuipers E.J., Laine L., Sung J., Tse F., et al. Management of Nonvariceal Upper Gastrointestinal Bleeding: Guideline Recommendations From the International Consensus Group. Ann Intern Med. 2019;171(11):805–22. DOI: 10.7326/M19-1795
70. Mayev I.V., Samsonov A.A., Andreev D.N. Gastrointestinal bleeding: symptoms, diagnosis and treatment. Farmateka.2014;2:47–53 (In Russ.) ISSN: 2414–9128
71. Almegren M. Reversal of direct oral anticoagulants. Vasc Health Risk Manag. 2017;13:287–92. DOI: 10.2147/VHRM.S138890
72. Tummala R., Kavtaradze A., Gupta A., Ghosh R.K. Specific antidotes against direct oral anticoagulants: A comprehensive review of clinical trials data. Int J Cardiol. 2016;214:292–8. DOI: 10.1016/j.ijcard.2016.03.056
73. Pollack C.V. Jr., Reilly P.A., van Ryn J., Eikelboom J.W., Glund S., Bernstein R.A., et. al Idarucizumab for Dabigatran Reversal — Full Cohort Analysis. N Engl J Med. 2017;377(5):431–41. DOI: 10.1056/NEJ-Moa1707278
74. Connolly S.J., Milling T.J. Jr., Eikelboom J.W., Gibson C.M., Curnutte J.T., Gold A., ANNEXA-4 Investigators. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med. 2016;375(12):1131–41. DOI: 10.1056/NEJMoa1607887
Review
For citations:
Lapina N.S., Alekseeva A.A., Vershinina A.D., Khruleva N.S., Muradova F.N., Koroleva L.Y. Gastrointestinal Bleeding in Antithrombotic Therapy in Patients with Coronary Heart Disease: Risk Factors, Pathogenesis and Treatment. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2020;30(3):14-23. (In Russ.) https://doi.org/10.22416/1382-4376-2020-30-3-14-23