Pathogenetic approaches to treatment of aspirin-induced gastroenteropathies in case of long-term intake of acetylsalicylic acid in patients with chronic ischemic heart disease


DOI: https://dx.doi.org/10.18565/therapy.2020.3.56-62

Borovkova N.Yu., Buyanova M.V., Bakka T.E., Nistratova M.P.

1 Privolzhsky Research Medical University of the Ministry of Healthcare of Russia, Nizhny Novgorod; 2 N.A. Semashko Nizhny Novgorod regional clinical hospital
The aim of the study: to assess the therapeutic efficacy of rebamipide from the perspective of pathogenetic approaches in the treatment of aspirin-induced gastroenteropathies (AIGEP) in patients with chronic coronary heart disease (CHD).
Material and methods. 340 patients with CHD were examined. They were receiving acetylsalicylic acid (ASA) therapy in a cardioprotective dosage for a long time. Selective coronary angiography was used for accurate verification of CHD. For AIGEP identification fibroesophagogastroduodenoscopy (FGDS) was performed, and the frequency and structure of this pathology were evaluated.For the treatment of AIGEP, a stimulator of the production of endogenous prostaglandins rebamipid was used in combination with a protopump inhibitor pantoprazole. The comparison group consisted of patients with CHD, in which AIGEP was treated with pantoprazole only. To clarify the pathogenetic mechanisms of the development of erosive and ulcerative lesions of the gastrointestinal tract during ASA administration, the level of prostaglandin E2 (PGE) and pro-inflammatory cytokines in the blood serum was determined before and after the treatment. The control group consisted of patients with CHD without AIGEP symptomes.
Results. From 340 patients with CHD, AIGEP was detected in 15% of cases. According to the results of endoscopic examination in patients with this pathology, it was fixed the prevailing of domination of erosive process in the body and antrum of the stomach. In patients with CHD and AIGEP, the level of PGE2 was significantly lower than in the control group, and the level of pro-inflammatory cytokines, on the contrary, was significantly increased. As a result of PPI treatment, a positive dynamics was observed in the endoscopic picture in 19 from 25 patients. At the same time, laboratory parameters had a tendency to normalize; however, these changes were statistically insignificant. Against the background of IPP intake, together with rebamipide, we managed to restore the mucous tunica condition in all examined patients, also significant positive changes in the level of PGE2 and the cytokine profile were observed.
Conclusion. The study demonstrated the features of AIGEP formation in CHD patients, designated possible ways for their correction.
Keywords: pro-inflammatory cytokines, aspirin-induced gastroenteropathies, rebamipid, prostaglandin E2, proton pump inhibitors, acetylsalicylic acid, coronary heart disease
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Literature


  1. Карпов Ю.А., Кухарчук В.В., Лякишев А.А. соавт. Диагностика и лечение хронической ишемической болезни сердца. Кардиологический вестник. 2015; 10(3): 3–33. [Karpov Yu.A., Kukharchuk V.V., Lyakishev A.A. et al. Diagnosis and treatment of chronic ischemic heart disease. Kardiologicheskiy vestnik. 2015; 10(3): 3–33 (In Russ.)].

  2. Кириченко А.А., Эбзеева Е.Ю. Ацетилсалициловая кислота при вторичной профилактике сердечно-сосудистых осложнений. Consilium Medicum. 2019; 21(5): 28–31. [Kirichenko A.A., Ebzeeva E.Yu. Acetylsalicylic acid in the secondary prevention of cardiovascular complications. Consilium Medicum. 2019; 21(5): 28–31 (In Russ.)]. doi: 10.26442/20751753.2019.5.190454.

  3. Hsu P.I., Tsai T.J. Epidemiology of upper gastrointestinal damage associated with low-dose aspirin. Curr Pharm Des. 2015; 21(35): 5049–55.

  4. Минушкина А.О. Проблемы безопасности при использовании препаратов ацетилсалициловой кислоты для профилактики сердечно-сосудистых осложнений. Сердце: журнал для практикующих врачей. 2014; 77(3): 173–178. [Minushkina A.O. Issues of aspirin safety in the prevention of cardiovascular complications. Serdtse: zhurnal dlya praktikuyuschikh vrachey. 2014; 77(3): 173–178 (In Russ.)].

  5. Каратеев А.Е., Насонов Е.Л., В.Т. Яхно Н.Н. с соавт. Клинические рекомендации «Рациональное применение нестероидных противовоспалительных препаратов (НПВП) в клинической практике». Современная ревматология. 2015; 1: 4–23. [Karateev A.E., Nasonov E.L., Yakhno N.N. et al. Clinical guidelines «Rational use of nonsteroidal anti-inflammatory drugs (NSAIDs) in clinical practice». Sovremennaya revmatologiya. 2015; 1: 4–23 (In Russ.)]. doi: 10.14412/1996-7012-2015-1-4-23.

  6. Бакулин И.Г., Сайганов С.А., Скалинская М.И. с соавт. Коморбидный пациент в гастроэнтерологии: индивидуальный подход. Рациональная фармакотерапия в кардиологии. 2018; 14(1): 65–69. [Bakulin I.G., Sayganov S.A., Skalinskaya M.I. et al. Comorbid patient in gastroenterology: individual approach. Ratsional'naya farmakoterapiya v kardiologii. 2018; 14(1): 65–69 (In Russ.)]. doi: 10.20996/1819-6446-2018-14-1-65-69.

  7. Свистунов А.А., Осадчук М.А., Киреева Н.В. с соавт. НПВП-индуцированная энтеропатия: современное состояние проблемы. Терапевтический архив. 2018; 08: 95–100. [Svistunov A.A., Osadchuk M.A., Kireeva N.V. et al. NSAID-induced enteropathy: the current state of the problem. Terapevticheskiy arkhiv. 2018; 08: 95–100 (In Russ.)]. doi: 10.26442/terarkh201890895-100.

  8. Naito Y., Yoshikawa T. Rebamipide: a gastrointestinal protective drug with pleiotropic activities. Expect Rev Gastroenterol Hepatol. 2010; 4(3): 261–70. doi: 10.1586/egh.10.25.

  9. Nagano Y., Matsui H., Muramatsu M., et.al. Rebamipide significantly inhibits indometacine-induced mitochondrial damage, lipid peroxidation, and apoptosis in gastric epithelial RGM-1 cells. Dig Dis Sci. 2005; 50(Suppl 1): 76–83.

  10. Li W., Zhao Y., Xu X. et. al. Rebamipide suppresses TNF-a mediated inflammation in vitro and attenuated the severity of dermatitis in mice. FEBS J. 2015; 282(12): 2317–26. doi: 10.1111/febs.13278.

  11. Болдуева С.А., Леонова И.А. Ацетилсалициловая кислота: все ли мы о ней знаем и правильно ли используем? Рациональная фармакотерапия в кардиологии. 2012; 8(5): 708–716. [Boldueva S.A., Leonova I.A. Acetylsalicylic acid: do we know everything about it and its proper use? Ratsional'naya farmakoterapiya v kardiologii. 2012; 8(5): 708–716 (In Russ.)].

  12. Маев И.В., Андреев Д.Н., Дичаева Д.Т. с соавт. Новые представления о гастропатии, ассоциированной с применением нестероидных противовоспалительных препаратов. Consilium medicum. 2017; 19(8): 8–14. [Maev I.V., Andreev D.N., Dicheva D.T. et al. New understanding about gastropathy associated with using of nonsteroidal anti-inflammatory drugs. Consilium medicum. 2017; 19(8): 8–14 (In Russ.)].

  13. Brzozowski Т., Konturek P.C., Konturek S.J. et al. Classic NSAID and selective COX-1 and COX 2 inhibition in healing chronic gastric ulcers. Microsc Res Tech. 2001; 53: 343–53.


About the Autors

Natalya Yu. Borovkova, MD, professor of the Department of hospital therapy and General medical practice named after V.G. Vogralik of Privolzhsky Research Medical University of the Ministry of Healthcare of Russia. Address: 603005, Nizhny Novgorod, 10/1 pl. Minin and Pozharsky Str. Tel.: +7 (910) 382-20-73. E-mail: borovkov-nn@mail.ru
Marina V. Buyanova, postgraduate student of the Department of hospital therapy and General medical practice named after V.G. Vogralik of Privolzhsky Research Medical University of the Ministry of Healthcare of Russia. Address: 603005, Nizhny Novgorod, 10/1 pl. Minin and Pozharsky Str. Tel.: +7 (908) 231-27-35. E-mail: buyanova.250@gmail.com
Tatyana E. Bakka, acting chief of the cardiology Department of N.A. Semashko Nizhny Novgorod regional clinical hospital. Address: 603126, Nizhny Novgorod, 190 Rodionova Str. Tel.: +7 (987) 399-53-86. E-mail: medik.89@list.ru
Marina P. Nistratova, chief of the laboratory diagnostics Department of N.A. Semashko Nizhny Novgorod regional clinical hospital. Address: 603126, Nizhny Novgorod, 190 Rodionova Str. Tel.: +7 (905) 012-86-38. E-mail: mary.nistratova@yandex.ru


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