Ключевые побочные эффекты антиагрегантов связаны с повреждающим действием на слизистую оболочку верхних отделов желудочно-кишечного тракта (ЖКТ) с развитием эрозий и язв, в том числе осложняющихся кровотечениями. Цель. Эндоскопическая и гистологическая оценка состояния слизистой оболочки верхних отделов ЖКТ у больных со стабильной ишемической болезнью сердца, длительно получающих антиагрегантную терапию и перенесших эпизод желудочно-кишечных кровотечений (ЖКК) либо имеющих высокий риск данного осложнения. Материалы и методы. Больные, включенные в исследование, являлись участниками одноцентрового проспективного регистра длительной антитромботической терапии РЕГАТА-1. Эндоскопическое исследование с биопсией слизистой оболочки желудка выполнено у 20 больных, перенесших эпизод ЖКК давностью менее 1 года, а также у 24 больных без ЖКК, но с сопутствующими факторами риска – эрозивно-язвенным анамнезом и/или стойкими явлениями диспепсии. Оценивали состояние слизистой (эрозии и язвы) по модифицированной шкале Ланца. При гистологическом исследовании определяли наличие Helicobacter pylori, оценивали характеристики воспалительного процесса в соответствии с модифицированной Сиднейской классификацией. Все больные на момент эзофагогастродуоденоскопии получали антитромботические препараты, ингибиторы протонной помпы назначались в 81,8% случаев. Исходный скрининг и эрадикация не проводились. Результаты. Наиболее частыми эндоскопическими находками являлись: хроническое воспаление (93,2%), атрофия (59,1%), а также множественные эрозии (45,5%) либо язвы (18,2%). Важным патогенетическим механизмом, поддерживающим повреждение слизистой оболочки ЖКТ, являлась инфекция H. pylori, обнаруженная в образцах слизистой у 90,9% больных. Заключение. У больных со стабильной ишемической болезнью сердца, принимающих антитромботические препараты и имеющих сопутствующие факторы риска ЖКК, эндоскопические признаки повреждения слизистой оболочки сохраняются, несмотря на длительную терапию ингибиторами протонной помпы. В основе указанных изменений может лежать контаминация H. pylori, что указывает на необходимость активного скрининга и эрадикации возбудителя у данной категории больных.
The key side effects of antiplatelet therapy are associated with the damage of the upper gastrointestinal tract (GIT) mucous that can lead to erosions or ulcers and specifically complicated by bleeding. Aim. To assess the upper gastrointestinal mucosal condition by endoscopic and histological methods in patients with stable coronary arteries disease receiving long-term antiplatelet therapy with gastrointestinal bleeding (GIB) history or with high risk of this complication. Materials and methods.The study included patients from the single-center prospective registry of long-term antithrombotic therapy REGATTA-1.
The gastric mucosa endoscopic examination with biopsy was performed in 20 patients with gastrointestinal bleeding history less than 1 year ago and in 24 patients without GIB, which have concomitant risk factors such as erosions and ulcers history and/or persistent dyspepsia clinical signs. The mucosal condition (erosions and ulcers) was estimated using a modified Lanz scale. The presence of Helicobacter pylori was determined by Histological verification. The inflammatory process characteristics were evaluated according to the modified Sydney classification. All participants received antithrombotic therapy at the time of esophagogastroduodenoscopy; 81.8% of patients received proton pump inhibitors. Results. Chronic inflammation (93.2%), atrophy (59.1%), multiple erosions (45.5%) or ulcers (18.2%) were the most frequent endoscopic finding. H. pylori infection, found in mucosal samples in 90.9% of patients was one of the most important pathogenesis mechanism, which support the gastrointestinal mucosa damage. Conclusion. Mucosal damage endoscopic signs remains despite long-term proton pump inhibitors therapy in patients with coronary arteries disease and concomitant GIB risk factors, receiving antithrombotic therapy. H. pylori contamination may be the cause of these changes. Тtherefore, its active screening and eradication is necessary in such patients.
1. Российское кардиологическое общество. Стабильная ишемическая болезнь сердца. Клинические рекомендации 2020. Рос. кардиол. журн. 2020;25(11):4076 [Russian Society of Cardiology (RSC). 2020 Clinical practice guidelines for Stable coronary artery disease. Russian Journal of Cardiology. 2020;25(11):4076 (in Russian)]. DOI:10.15829/29/1560-4071-2020-4076
2. Sehested TSG, Carlson N, Hansen PW, et al. Reduced risk of gastrointestinal bleeding associated with proton pump inhibitor therapy in patients treated with dual antiplatelet therapy after myocardial infarction. Eur Heart J. 2019;40(24):1963-70.
DOI:10.1093/eurheartj/ehz104
3. Шахматова О.О., Комаров А.Л., Коробкова В.В., и др. Кровотечения из верхних отделов желудочно-кишечного тракта у пациентов со стабильной ишемической болезнью сердца (по результатам проспективного РЕГистра длительной Антитромботической ТерАпии – РЕГАТА). Терапевтический архив. 2020;92(9):30-8 [Shakhmatova OO, Komarov AL, Korobkova VV, et al. Upper gastrointestinal bleeding in patients with stable coronary artery disease (registry of antithrombotic therapy “REGATТA” results). Terapevticheskii Arkhiv (Ter. Arkh.). 2020;92(9):30-8 (in Russian)].
DOI:10.26442/00403660.2020.09.000699
4. Комаров А.Л., Шахматова О.О., Коробкова В.В., и др. Факторы риска и исходы желудочно-кишечных кровотечений у больных стабильной ишемической болезнью сердца: данные наблюдательного регистра длительной антитромботической терапии РЕГАТА-1. Рос. кардиол. журн. 2021;26(6):4465 [Komarov AL, Shakhmatova OO, Korobkova VV, et al. Risk factors and outcomes of upper gastro-intestinal bleedings in patients with stable CAD: the observational registry of long-term antithrombotic therapy REGATTA-1 data. Russian Journal of Cardiology. 2021;26(6):4465 (in Russian)]. DOI:10.15829/1560-4071-2021-4465
5. Barkun AN, Almadi M, Kuipers EJ, 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
6. Gralnek IM, Dumonceau JM, Kuipers EJ, et al. Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2015;47:1-46. DOI:10.1055/s-0034-1393172
7. Lanza FL, Collaku A, Liu DJ. Endoscopic comparison of gastroduodenal injury with over-the-counter doses of new fast-dissolving ibuprofen and paracetamol formulations: a randomized, placebo-controlled, 4-way crossover clinical trial. Clin Exp Gastroenterol. 2018;11:169-77. DOI:10.2147/CEG.S153231
8. Dixon MF, Genta RM, Yardley JH. Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 1996;20:1161-81. DOI:10.1097/00000478-199610000-00001
9. Malfertheiner P, Megraud F, O’Morain CA, et al. Management of Helicobacter Pylori infection – the Maastricht V/Florence Consensus Report. Gut. 2017;66(1):6-30. DOI:10.1136/gutjnl-2016-312288
10. Lanas A, Dumonceau JM, Hunt RH, et al. Non-variceal upper gastrointestinal bleeding. Nat Rev Dis Primers. 2018;4:18020. DOI:10.1038/nrdp.2018.20
11. Cryer B, Bhatt DL, Lanza FL, et al. Low-dose aspirin-induced ulceration is attenuated by aspirin-phosphatidylcholine: a randomized clinical trial. Am J Gastroenterol. 2011;106(2):272-7. DOI:10.1038/ajg.2010.436
12. Mahady SE, Margolis KL, Chan A, et al. Major GI bleeding in older persons using aspirin: incidence and risk factors in the ASPREE randomised controlled trial. Gut. 2021;70:717-24. DOI:10.1136/gutjnl-2020-321585
13. Negovan A, Moldovan V, Iancu V, et al. The contribution of clinical and pathological predisposing factors to severe gastro-duodenal lesions in patients with long-term low-dose aspirin and proton pump inhibitor therapy. Eur J Intern Med. 2017;44:62-6. DOI:10.1016/j.ejim.2017.05.017
14. Li Z, Wu C, Li L, et al. Effect of long-term proton pump inhibitor administration on gastric mucosal atrophy: A meta-analysis. Saudi
J Gastroenterol. 2017;23(4):222-8. DOI:10.4103/sjg.SJG_573_16
15. Gralnek IM, Stanley AJ, Morris AJ, et al. Endoscopic diagnosis and management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH): European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2021. Endoscopy. 2021;53(3):300-32. DOI:10.1055/a-1369-5274
16. El-Serag HB, Kao JY, Kanwal F, et al. Houston Consensus Conference on testing for Helicobacter Pylori infection in the United States. Clin Gastroenterol Hepatol. 2018;16(7):992-1002.e6.
DOI:10.1016/j.cgh.2018.03.013
17. Mezmale L, Coelho LG, Bordin D, et al. Epidemiology of Helicobacter Pylori. Helicobacter. 2020;25(Suppl. 1):e12734. DOI:10.1111/hel.12734
18. Na’amnih W, Ben Tov A, Bdair-Amsha A. Physicians’ adherence to management guidelines for H. pylori infection and gastroesophageal reflux disease: a crosssectional study. Isr J Health Policy Res. 2020;9:28. DOI:10.1186/s13584-020-00389-y
19. Song C, Xie C, Zhu Y. Management of Helicobacter Pylori infection by clinicians: A nationwide survey in a developing country. Helicobacter. 2019;24:e12656. DOI:10.1111/hel.12656
20. Steffel J, Collins R, Antz M, et al. 2021 European Heart Rhythm Association Practical Guide on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation. Europace. 2021:euab065. DOI:10.1093/europace/euab065
21. Richard W. Goodgame. Viral Infections of the Gastrointestinal Tract. Curr Gastroenterol Rep. 1999;1:292-300. DOI:10.1007/s11894-999-0112-5
22. Iwamuro M, Kondo E, Tanaka T, et al. Endoscopic Manifestations and Clinical Characteristics of Cytomegalovirus Infection in the Upper Gastrointestinal Tract. Acta Med Okayama. 2017;71(2):97-104. DOI:10.18926/AMO/54977
23. Darmon A, Sorbets E, Ducroc G, et al. Association of Multiple Enrichment Criteria With Ischemic and Bleeding Risks Among COMPASS-Eligible Patients. J Am Coll Cardiol. 2019;73(25):3281-91. DOI:10.1016/j.jacc.2019.04.046
24. Savarino V, Dulbecco P, de Bortoli N, et al. The appropriate use of proton pump inhibitors (PPIs): Need for a reappraisal. Eur J Intern Med. 2017;37:19-24. DOI:10.1016/j.ejim.2016.10.007
25. Jaynes M, Kumar AB. The risks of long-term use of proton pump inhibitors: a critical review. Ther Adv Drug Saf. 2019;10:1-3. DOI:10.1177/2042098618809927
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1. Russian Society of Cardiology (RSC). 2020 Clinical practice guidelines for Stable coronary artery disease. Russian Journal of Cardiology. 2020;25(11):4076 (in Russian). DOI:10.15829/29/1560-4071-2020-4076
2. Sehested TSG, Carlson N, Hansen PW, et al. Reduced risk of gastrointestinal bleeding associated with proton pump inhibitor therapy in patients treated with dual antiplatelet therapy after myocardial infarction. Eur Heart J. 2019;40(24):1963-70.
DOI:10.1093/eurheartj/ehz104
3. Shakhmatova OO, Komarov AL, Korobkova VV, et al. Upper gastrointestinal bleeding in patients with stable coronary artery disease (registry of antithrombotic therapy “REGATТA” results). Terapevticheskii Arkhiv (Ter. Arkh.). 2020;92(9):30-8 (in Russian).
DOI:10.26442/00403660.2020.09.000699
4. Komarov AL, Shakhmatova OO, Korobkova VV, et al. Risk factors and outcomes of upper gastro-intestinal bleedings in patients with stable CAD: the observational registry of long-term antithrombotic therapy REGATTA-1 data. Russian Journal of Cardiology. 2021;26(6):4465 (in Russian). DOI:10.15829/1560-4071-2021-4465
5. Barkun AN, Almadi M, Kuipers EJ, 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
6. Gralnek IM, Dumonceau JM, Kuipers EJ, et al. Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2015;47:1-46. DOI:10.1055/s-0034-1393172
7. Lanza FL, Collaku A, Liu DJ. Endoscopic comparison of gastroduodenal injury with over-the-counter doses of new fast-dissolving ibuprofen and paracetamol formulations: a randomized, placebo-controlled, 4-way crossover clinical trial. Clin Exp Gastroenterol. 2018;11:169-77. DOI:10.2147/CEG.S153231
8. Dixon MF, Genta RM, Yardley JH. Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 1996;20:1161-81. DOI:10.1097/00000478-199610000-00001
9. Malfertheiner P, Megraud F, O’Morain CA, et al. Management of Helicobacter Pylori infection – the Maastricht V/Florence Consensus Report. Gut. 2017;66(1):6-30. DOI:10.1136/gutjnl-2016-312288
10. Lanas A, Dumonceau JM, Hunt RH, et al. Non-variceal upper gastrointestinal bleeding. Nat Rev Dis Primers. 2018;4:18020. DOI:10.1038/nrdp.2018.20
11. Cryer B, Bhatt DL, Lanza FL, et al. Low-dose aspirin-induced ulceration is attenuated by aspirin-phosphatidylcholine: a randomized clinical trial. Am J Gastroenterol. 2011;106(2):272-7. DOI:10.1038/ajg.2010.436
12. Mahady SE, Margolis KL, Chan A, et al. Major GI bleeding in older persons using aspirin: incidence and risk factors in the ASPREE randomised controlled trial. Gut. 2021;70:717-24. DOI:10.1136/gutjnl-2020-321585
13. Negovan A, Moldovan V, Iancu V, et al. The contribution of clinical and pathological predisposing factors to severe gastro-duodenal lesions in patients with long-term low-dose aspirin and proton pump inhibitor therapy. Eur J Intern Med. 2017;44:62-6. DOI:10.1016/j.ejim.2017.05.017
14. Li Z, Wu C, Li L, et al. Effect of long-term proton pump inhibitor administration on gastric mucosal atrophy: A meta-analysis. Saudi
J Gastroenterol. 2017;23(4):222-8. DOI:10.4103/sjg.SJG_573_16
15. Gralnek IM, Stanley AJ, Morris AJ, et al. Endoscopic diagnosis and management of nonvariceal upper gastrointestinal hemorrhage (NVUGIH): European Society of Gastrointestinal Endoscopy (ESGE) Guideline – Update 2021. Endoscopy. 2021;53(3):300-32. DOI:10.1055/a-1369-5274
16. El-Serag HB, Kao JY, Kanwal F, et al. Houston Consensus Conference on testing for Helicobacter Pylori infection in the United States. Clin Gastroenterol Hepatol. 2018;16(7):992-1002.e6.
DOI:10.1016/j.cgh.2018.03.013
17. Mezmale L, Coelho LG, Bordin D, et al. Epidemiology of Helicobacter Pylori. Helicobacter. 2020;25(Suppl. 1):e12734. DOI:10.1111/hel.12734
18. Na’amnih W, Ben Tov A, Bdair-Amsha A. Physicians’ adherence to management guidelines for H. pylori infection and gastroesophageal reflux disease: a crosssectional study. Isr J Health Policy Res. 2020;9:28. DOI:10.1186/s13584-020-00389-y
19. Song C, Xie C, Zhu Y. Management of Helicobacter Pylori infection by clinicians: A nationwide survey in a developing country. Helicobacter. 2019;24:e12656. DOI:10.1111/hel.12656
20. Steffel J, Collins R, Antz M, et al. 2021 European Heart Rhythm Association Practical Guide on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation. Europace. 2021:euab065. DOI:10.1093/europace/euab065
21. Richard W. Goodgame. Viral Infections of the Gastrointestinal Tract. Curr Gastroenterol Rep. 1999;1:292-300. DOI:10.1007/s11894-999-0112-5
22. Iwamuro M, Kondo E, Tanaka T, et al. Endoscopic Manifestations and Clinical Characteristics of Cytomegalovirus Infection in the Upper Gastrointestinal Tract. Acta Med Okayama. 2017;71(2):97-104. DOI:10.18926/AMO/54977
23. Darmon A, Sorbets E, Ducroc G, et al. Association of Multiple Enrichment Criteria With Ischemic and Bleeding Risks Among COMPASS-Eligible Patients. J Am Coll Cardiol. 2019;73(25):3281-91. DOI:10.1016/j.jacc.2019.04.046
24. Savarino V, Dulbecco P, de Bortoli N, et al. The appropriate use of proton pump inhibitors (PPIs): Need for a reappraisal. Eur J Intern Med. 2017;37:19-24. DOI:10.1016/j.ejim.2016.10.007
25. Jaynes M, Kumar AB. The risks of long-term use of proton pump inhibitors: a critical review. Ther Adv Drug Saf. 2019;10:1-3. DOI:10.1177/2042098618809927