Natalia Yu. Borovkova , Marina V. Buyanova
Abstract
Multidisciplinary approach to safety of antithrombotic therapy used in clinical practice is reported. Such complications of antithrombotic therapy as gastrointestinal tract (GIT) erosion/ulceration and gastrointestinal bleeding are discussed in detail. The modern pathogenetically substantiated methods of gastric mucosa protection based on the use of rebamipide, the GIT mucosal protector agent with proven efficacy, are proposed.
Key words: antithrombotic therapy, gastrointestinal bleeding, gastroenteroprotection, rebamipide.
Key words: antithrombotic therapy, gastrointestinal bleeding, gastroenteroprotection, rebamipide.
About the Author
Natalia Yu. Borovkova 1 , Marina V. Buyanova 11 Privolzhsky Research Medical University, Nizhny Novgorod, Russia
References
1. Stabil'naia ishemicheskaia bolezn' serdtsa. Klinicheskie rekomendatsii. Minzdrav Rossii. Moscow, 2020 (in Russian).
2. Ostryi infarkt miokarda s pod"emom segmenta ST na elektrokardiogramme. Klinicheskie rekomendatsii. Minzdrav Rossii. Moscow, 2020 (in Russian).
3. Fibrilliatsiia i trepetanie predserdii. Klinicheskie rekomendatsii. Odobreno na zasedanii Nauchno-prakticheskogo soveta Minzdravf Rossii (zasedanie ot 16.10.2020, protokol №38/2-3-4). Moscow, 2020 (in Russian).
4. Eikelboom JW, Connolly SJ, Bosch J et al. COMPASS Investigators. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med 2017; 377: 1319–30. DOI: 10.1056/NEJMoa1709118
5. Downloaded from https://academic.oup.com/europace/advance-article/doi/10.1093/europace/euab065/6247378 by guest on 01 May 2021.
6. Tarasova L.V., Dimitrieva O.V., Busalaeva E.I. Gastroduodenal'nye riski pri terapii novymi oral'nymi antikoaguliantami i vozmozhnosti ikh minimizatsii. Meditsinskii alfavit. 2020 (13): 26–32. DOI: 10.33667/2078-5631-2020-13-26-32 (in Russian).
7. Moroz E.V., Karateev A.E., Kriukov E.V., Chernetsov V.A. Gastrointestinal bleeding with the use of new oral anticoagulants: epidemiology, risk factors, treatment, and prevention. Nauchno-prakticheskaia revmatologiia. 2017; 55 (6): 675–84 (in Russian).
8. Hsu PI, Tsai TJ. Epidemiology of Upper Gastrointestinal Damage Associated with Low-Dose Aspirin. Curr Pharm Des 2015; 21 (35): 5049–55. DOI: 10.2174/1381612821666150915104800
9. Borovkova N.Iu., Buianova M.V., Terekhova V.V. et al. Osobennosti aspirinindutsirovannykh porazhenii zheludochno-kishechnogo trakta u bol'nykh khronicheskoi ishemicheskoi bolezn'iu serdtsa i vozmozhnye puti ikh korrektsii. Kardiovaskuliarnaia terapiia i profilaktika. 2020; 19 (2): 2463. DOI: 10.15829/1728-8800-2020-2-2463 (in Russian).
10. Garcia Rodriguez LA, Martin-Perez M, Hennekens CH et al. Bleeding Risk with Long-Term LowDose Aspirin: A Systematic Review of Observational Studies. PLoS One 2016; 11 (8): e0160046. DOI: 10.1371/journal.pone.0160046
11. Laine L. Review article: gastrointestinal bleeding with low-dose aspirin – what’s the risk? Aliment Pharmacol Ther 2006; 24: 897–908. DOI: 10.1111/j.1365-2036.2006.03077.x
12. Sorensen HT, Mellemkjaer L, Blot WJ et al. Risk of upper gastrointestinal bleeding associated with use of low-dose aspirin. Am J Gastroenterol 2000; 95: 2218–24. DOI: 10.1111/j.1572-0241.2000. 02248.x
13. Watari I, Oka S et al. Effectiveness of polaprezinc for low-dose aspirin-induced small-bowel mucosal injuries as evaluated by capsule endoscopy: a pilot randomized controlled study. BMC Gastroenterol 2013; 13: 108. DOI: 10.1186/1471-230X-13-108
14. Watari I, Oka S, Tanaka S et al. Comparison of small-bowel mucosal injury between low-dose aspirin and nonaspirin non-steroidal anti-Inflammatory drugs: a capsule endoscopy study. Digestion 2014; 89 (3): 225–31.
15. Endo H, Hosono K, Inamori M et al. Incidence of small bowel injury induced by low-dose aspirin: a crossover study using capsule endoscopy in healthy volunteers. Digestion 2009; 79 (1): 44–51.
16. Ushkalova E.A. Klinicheskaia farmakologiia sovremennykh antatsidov. Farmateka. 2006; 126 (11): 24–31 (in Russian).
17. Karateev A.E., Moroz E.V. Problema NPVP-gastropatii. Sovremennye predstavleniia. Meditsinskii alfavit. 2017; 4 (40): 13–20 (in Russian).
18. Vlasova T.V., Shkarin V.V., Solov'eva E.V. Kardiovaskuliarnye i gastrointestinal'nye sviazi: prognosticheskaia znachimost' v bol'nogo et al. Meditsinskii sovet. 2017; 7: 98–101 (in Russian).
19. Pakhomova I.G., Khoroshinina L.P. Kak minimizirovat' riski NPVP-indutsirovannykh porazhenii ZhKT? Vozmozhnaia taktika vedeniia patsienta. Meditsinskii alfavit. 2017; 1 (8): 15–23 (in Russian).
20. Watanabe T, Fujiwara Y, Chan Watanabe F et al. Current knowledge on non-steroidal anti-inflammatory druginduced small-bowel damage: a comprehensive review. J Gastroenterol 2019; 55: 105–10. DOI: 10.1007/s00535-019-01657-8
21. Kim V.A. NPVP-gastropatiia i rol' prostaglandinov v ee vozniknovenii, profilaktike i lechenii. Eksperimental'naia i klinicheskaia gastroenterologiia. 2008; 8: 84–91 (in Russian).
22. Emelina E.I. Kardiomagnil: uluchshenie priverzhennosti k lecheniiu za schet snizheniia chastoty pobochnykh effektov. Atmosfera. Novosti kardiologii. 2011; 1: 14–8 (in Russian).
23. Borovkova N.Iu., Buianova M.V., Bakka T.E. et al. Vozmozhnosti lecheniia aspirin-indutsirovannykh porazhenii zheludka i dvenadtsatiperstnoi kishki u patsientov s khronicheskoi ishemicheskoi bolezn'iu serdtsa. Klinicheskaia meditsina. 2020; 98 (3): 231–35. DOI: 10.30629/0023-2149-2020-98-3-231-235 (in Russian).
24. Levykh A.E. Atsetilsalitsilovaia kislota kak effektivnaia i bezopasnaia osnova antiagregantnoi terapii. Arterial'naia gipertenziia. 2015; 44 (6): 57–63 (in Russian).
25. Pakhomova I.G. NPVP-assotsiirovannye povrezhdeniia zheludochno-kishechnogo trakta i ikh oslozhneniia: puti profilaktiki. Consilium Medicum. 2017; 19 (9): 109–13 (in Russian).
26. Minushkina A.O. Problemy bezopasnosti pri ispol'zovanii preparatov atsetilsalitsilovoi kisloty dlia profilaktiki serdechno-sosudistykh oslozhnenii. Serdtse: zhurnal dlia praktikuiushchikh vrachei. 2014; 13 (3): 173–78 (in Russian).
27. Ota K, Takeuchi T, Kojima Yet al. Preventive effect of ecabet sodium on low-dose aspirin-induced small intestinal mucosal injury: a randomized, double-blind, pilot study. BMC Gastroenterology 2019; 1. DOI: 10.1186/s12876-018-0923-7
28. Wallace JL. Prostaglandins NSAIDs and gastric mucosal protection: why doesn't the stomach digest itself? Physiolog Rev 2008; 88 (4): 1547–65.
29. Babak S.V., Bakunin I.G., Balukova E.V. et al. Porazheniia organov pishchevareniia, indutsirovannye priemom nesteroidnykh protivovospalitel'nykh preparatov. Saint Petersburg: InformMed, 2013. ISBN 978-5-904192-62-4 (in Russian).
30. Maev I.V., Samsonov A.A., Andreev D.N. Bolezni zheludka: monografiia. Moscow: GEOTAR-Media, 2015. ISBN 978-5-9704-3388-1 (in Russian).
31. Kliaritskaia I.L., Moshko Iu.A., Balabantseva A.P. et al. Patologiia gastroduodenal'noi zony, indutsirovannaia NPVP i terapevticheskaia taktika. Krymskii terapevticheskii zhurnal. 2017; 1: 5–15 (in Russian).
32. Lip G, Keshishian A, Li X et al. Effectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation Patients. Stroke 2018; 49 (12): 2933–44.
33. Patel MR, Mahaffey KW, Garg J et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365: 883–91. DOI: 10.1056/NEJMoa1009638
34. 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 (21): 2271–81. DOI: 10.1016/j.jacc.2015.09.024
35. Hindricks G et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2020; ehaa612. DOI: 10.1093/eurheartj/ehaa612
36. Delaney JA, Opatrny L, Brophy JM, Suissa S. Drug drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding. CMAJ 2007; 177 (4): 347–51. DOI: 10.1503/cmaj.
070186
37. Oakland K et al. Rebleeding and Mortality After Lower Gastrointestinal Bleeding in Patients Taking Antiplatelets or Anticoagulants. Clin Gastroenterol Hepatol 2019; 17 (7): 1276–84.e3.
38. Lopes RD, Heizer G, Aronson R et al. Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation. N Engl J Med 2019; 380: 1509–24. . DOI: 10.1056/NEJMoa1817083
39. Henry DA, Dobson C. Turner Variability in the risk of major gastrointestinal complications from nonsteroidal anti-inflammatory drugs. Gastroenterology 1993; 105 (4): 1078–88.
40. Lazebnik L.B., Bordin D.S., Tkachenko E.I. et al. Lekarstvennye gastroenteropatii (rekomendatsii po profilaktike i lecheniiu gastroenteropatii, indutsirovannykh nesteroidnymi protivovospalitel'nymi preparatami). Terapiia. 2018; 20 (2): 18–33 (in Russian).
41. Endo H, Sakai E, Higurashi T et al. Differences in the severity of small bowel mucosal injury based on the type of aspirin as evaluated by capsule endoscopy. Dig Liver Dis 2012; 44 (10): 833–8.
42. Ushkalova E.A. Aspirinorezistentnost': mekhanizmy razvitiia, metody opredeleniia i klinicheskoe znachenie. Farmateka. 2006; 128 (13): 35–41 (in Russian).
43. Goodman LA. Gilman Goodman and Gilman`s the pharmacological basis of therapeutics. 8 ed. New York: Pergamon press, 1990: 1811 p. ISBN 0-08-040296-8
44. Bhatt D, Scheiman J, Abraham N et al. ACCF/ACG/AHA 2008 Expect 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. J Am College Cardiol 2008; 52 (18): 1502–17.
45. Taha AS, McCloskey C, Prasad R et al. Famotidine for the prevention of peptic ulcers and oesophagitis in patients taking low-dose aspirin (FAMOUS): a phase III, randomized, double-blind, placebo-controlled trial. Lancet 2009; 374 (9684): 119–25.
46. Klinicheskie rekomendatsii Rossiiskoi gastroenterologicheskoi assotsiatsii po diagnostike i lecheniiu erozivno-iazvennykh porazhenii zheludka, vyzvannykh priemom nesteroidnykh protivovospalitel'nykh preparatov. Ros. zhurn. gastroenterologii, gepatologii, koloproktologii. 2014; 6: 89–94 (in Russian).
47. Pozzoli C, Menozzi A, Grandi D et al. Protective effects of proton pump inhibitors against indomethacin-induced lesions in the rat small intestine. Naunyn Schmiedebergs Arch Pharmacol 2017; 374 (4): 283–91. DOI: 10.1007/s00210-006-0121-y
48. Moroz E.V., Karateev A.E. Rebamipid: effektivnaia medikamentoznaia profilaktika NPVP-enteropatii vozmozhna. Sovremennaia revmatologiia. 2016; 10 (4): 97–105 (in Russian).
49. Clooney AG, Bernstein CN, Leslie WD. A comparison of the gut microbiome between long-term users and non-users of proton pump inhibitors. Alimentary Pharmacol Therapeut 2016; 43 (9): 974–84.
50. Nadatani Y, Watanabe T, Suda W. Gastric acid inhibitor aggravates indomethacin-induced small intestinal injury via reducing Lactobacillus Johnsonii. Scientific Reports 2019: 17490.
51. Wallace J, Syer S, Denou E et al. Proton pump inhibitors exacerbate NSAID-induced small intestinal injury by inducing dysbiosis. Gastroenterology 2011; 141 (4): 1314–22.
52. Sostres С et al. Risk of rebleeding, vascular events and death after gastrointestinal bleeding in anticoagulant and/or antiplatelet users. Alimentary Pharmacol Terapeut 2019; 50 (8): 919–29.
53. Koch N. Non-steroidal anti-inflammatory drug gastropathy: clinical results with misoprostol. Ital J Gastroenterol Hepatol 1999; 31 (1): 54–62.
54. Silverstein FE., Graham DY, Senior JR.et al. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial. Annals Int Med 1995; 123 (4): 241–499.
55. Hawkey C, Karrasch J., Szczepanski L. et al. Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. New England J Med 1998; 338 (11): 727–34.
56. Rostom A, Dube C, Wells G et al. Prevention of NSAID-induced gastroduodenal ulcers: review [art. № CD002296]. Cochrane Database Systematic Rev. 2002; 4.
57. Goldstein J, Huang B, Amer F et al. Ulcer recurrence in high-risk patients receiving nonsteroidal anti-inflammatory drugs plus low-dose aspirin: results of a post hoc subanalysis. Clin Therapeut 2004; 26 (10): 1637–43.
58. Park SH, Cho CS, Lee OY et al. Comparison of prevention of NSAIDinduced gastrointestinal complications by rebamipide and misoprostol: a randomized, multicenter, controlled trial-STORM STUDY. J Clin Biochem Nutr 2007; 40 (2): 148–55. DOI: 10.3164/jcbn.40.148
59. Becker J, Domschke W, Pohle T. Current approaches to prevent NSAID-induced gastropathy – COX selectivity and beyond. British J Clin Pharmacol 2004; 58 (6): 587–600.
60. Watanbe T, Sugimore S, Kameda N et al. Small bowel injury by low-dose entericcoated aspirin and treatment with misoptostol: a pilot study. Clin Gastroenterol Hepatol 2008; 6 (11): 1279–82. DOI: 10.1016/j.cgh.2008.06.021
61. Kohata Y, Nakahara K, Tanigawa T et al. Rebamipide alters the esophageal microbiome and reduces the incidence of Barrett's esophagus in a rat model. Dig Dis Sci 2015; 60 (9): 2654–61. DOI: 10.1007/s10620-015-3662-4
62. Moon SJ, Park JS, Woo YJ et al. Rebamipide suppresses collagen-induced arthritis through reciprocal regulation of th17/treg cell differentiation and hemeoxygenase 1 induction. Arthritis Rheumatol 2014; 66 (4): 874–85. DOI: 10.1002/art.38310
63. Zvyaglova M.Yu., Knyazev O.V., Parfenov A.I. Pharmacological and clinical feature of rebamipide: new therapeutic targets. Therapeutic Archive. 2020; 92 (2): 104–11. (in Russian).
64. Naito Y, Yoshikawa T. Rebamipide: a gastrointestinal protective drug with pleiotropic activities. Expert Rev Gastroenterol Hepatol 2010; 4 (3): 261–70. DOI: 10.1586/egh.10.25
65. Kinjo N, Kawanaka H, Akahoshi T et al. Significance of ERK nitration in portal hypertensive gastropathy and its therapeutic implications. Amn J Physiol Gastrointestinal Liver Physiology 2008; 295 (5): G1016–G1024.
66. Abe N, Funato H, Hirata A. Evaluation of gastric mucosal injury model animals of rebamipide formulationstudy of therapeutic equivalence. Yakugaku Zasshi 2016; 136 (4): 677–84.
67. Hayashi S, Sugiyama T, Amano K et al. Effect of rebamipide, a novel antiulcer agent, on Helicobacter pylori adhesion to gastric epithelial cells. Antimicrobial Agents Chemotherapy 1998; 42 (8): 1895–99.
68. Nishizawa T, Nishizawa Y, Yahagi N et al. Effect of supplementation with rebamipide for Helicobacter pylori eradication therapy: a systematic review and meta-analysis. J Gastroenterol Hepatol 2014; 29 (4): 20–4.
69. Li W, Zhao Y, Xu X et al. Rebamipide suppresses TNF-α mediated inflammation in vitro and attenuates the severity of dermatitis in mice. FEBS J 2015; 282 (12): 2317–26. DOI: 10.1111/febs.13278
70. Iijima K, Ichikawa T, Okada S et al. Rebamipide, a cytoprotective drug, increases gastric mucus secretion in human: evaluations with endoscopic gastrin test. Digestive Diseases Sci 2009; 54 (7): 1500–7.
71. Akagi S, Fujiwara T, Nishida M et al. The effectiveness of rebamipide mouthwash therapy for radiotherapy and chemoradiotherapy-induced oral mucositis in patients with head and neck cancer: a systematic review and meta-analysis. J Pharm Health Care Sci 2019; 5: 16. DOI: 10.1186/s40780-019-0146-2
72. Tomita T, Sadakata T, Tamura M et al. Indomethacin-induced generation of reactive oxygen species leads to epithelial cell injury before the formation of intestinal lesions in mice. J Physiol Pharmacol 2014; 65 (3): 435–40.
73. Kurata S, Nakashima T, Osaki T et al. Rebamipide protects small intestinal mucosal injuries caused by indomethacin by modulating intestinal microbiota and the gene expression in intestinal mucosa in a rat model. J Clin Biochem Utrition 2015; 56 (1): 20–7.
74. Zhang S, Qing Q, Bai Y et al. Rebamipide helps defend against nonsteroidal anti-inflammatory drugs induced gastroenteropathy: a systematic review and meta-analysis. Dig Diseases Scien 2013; 58 (7): 1991–2000.
75. Kaziulin A.N. Goncharenko A.Iu., Mamaev I.V. Ispol'zovanie rebamipida v kachestve gastroprotektivnogo i protivovospalitel'nogo preparata pri NPVP-gastropatiiakh. Lechebnoe delo. 2016; 3: 50–8 (in Russian).
76. Yamamoto T, Isono A, Mishina Y et al. Gastroduodenal mucosal injury in patients taking low-dose aspirin and the role of gastric mucoprotective drugs: possible effect of rebamipide. J Clin Biochem Nutrition 2010; 47 (1): 27–31.
77. Ono S, Kato M, Imai A et al. Preliminary trial of rebamipide for prevention of low-dose aspirin-induced gastric injury in healthy subjects: a randomized, double-blind, placebo-controlled, cross-over study. J Clin Biochem Nutrition 2009; 45 (2): 248–53.
78. Tozawa K, Oshima T, Okugawa T et al. A randomized, double-blind, placebo-controlled study of rebamipide for gastric mucosal injury taking aspirin with or without clopidogrel. Dig Dis Scien 2014; 59: (8) 1885–90.
79. Watande N, Takeuchi T, Handa O et al. A multicenter, randomized, double-blind, placebo-controlled trial of high-dose rebamipide treatment for low-dose aspirin-induced moderate-to-severe small intestinal damage. PLoS one 2015; 10 (4): e0122330.
80. Kim JH, Park SH, Cho CS et al. Preventive efficacy and safety of rebamipide in nonsteroidal anti-inflammatory drug-induced mucosal toxicity. Gut Liver 2014; 8 (4): 371–9.
81. Borovkova N.Iu., Buianova M.V., Bakka T.E. et al. Patogeneticheskie podkhody k lecheniiu aspirinindutsirovannykh gastroenteropatii pri dlitel'nom prieme atsetilsalitsilovoi kisloty u bol'nykh s khronicheskoi ishemicheskoi bolezn'iu serdtsa. Terapiia. 2020; 3 (37): 56–62. DOI 10.18565/therapy.2020.3.56-62 (in Russian).
82. Takeshi Yamashita et al. Observational study of the effects of dabigatran on gastrointestinal symptoms in patients with non-valvular atrial fibrillation. J Arrhythmia 2014; 30 (December): 478–84.
For citation:Borovkova N.Yu., Buyanova M.V. Multidisciplinary approach to safety of antithrombotic therapy: focus on the gastrointestinal tract. Clinical review for general practice. 2021; 4: 51–59. DOI: 10.47407/kr2021.2.4.00060
All accepted articles publish licensed under a Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.
