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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="review-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Consilium Medicum</journal-id><journal-title-group><journal-title xml:lang="en">Consilium Medicum</journal-title><trans-title-group xml:lang="ru"><trans-title>Consilium Medicum</trans-title></trans-title-group><trans-title-group xml:lang="zh"><trans-title>Consilium Medicum</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2075-1753</issn><issn publication-format="electronic">2542-2170</issn><publisher><publisher-name xml:lang="en">Consilium Medicum</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">567876</article-id><article-id pub-id-type="doi">10.26442/20751753.2023.5.202294</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Articles</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Статьи</subject></subj-group><subj-group subj-group-type="article-type"><subject>Review Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Gastroprotective therapy in patients with atrial fibrillation receiving anticoagulant therapy: A review</article-title><trans-title-group xml:lang="ru"><trans-title>Гастропротективная терапия у пациентов с фибрилляцией предсердий, получающих антикоагулянтную терапию</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0795-8225</contrib-id><contrib-id contrib-id-type="spin">3910-6585</contrib-id><name-alternatives><name xml:lang="en"><surname>Ostroumova</surname><given-names>Olga D.</given-names></name><name xml:lang="ru"><surname>Остроумова</surname><given-names>Ольга Дмитриевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>D. Sci. (Med.), Prof.</p></bio><bio xml:lang="ru"><p>д-р мед. наук, проф., зав. каф. терапии и полиморбидной патологии им. акад. М.С. Вовси, проф. каф. клинической фармакологии и пропедевтики внутренних болезней</p></bio><email>ostroumova.olga@mail.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-5801-3742</contrib-id><contrib-id contrib-id-type="spin">9212-6010</contrib-id><name-alternatives><name xml:lang="en"><surname>Kochetkov</surname><given-names>Aleksey I.</given-names></name><name xml:lang="ru"><surname>Кочетков</surname><given-names>Алексей Иванович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Cand. Sci. (Med.), Assoc. Prof.</p></bio><bio xml:lang="ru"><p>канд. мед. наук, доц., доц. каф. терапии и полиморбидной патологии им. акад. М.С. Вовси</p></bio><email>ak_info@list.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1316-7654</contrib-id><name-alternatives><name xml:lang="en"><surname>Batyukina</surname><given-names>Svetlana V.</given-names></name><name xml:lang="ru"><surname>Батюкина</surname><given-names>Светлана Владимировна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Graduate Student</p></bio><bio xml:lang="ru"><p>аспирант 3-го года каф. терапии и полиморбидной патологии им. акад. М.С. Вовси</p></bio><email>batyukina.svetlana@yandex.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0982-2006</contrib-id><contrib-id contrib-id-type="spin">5861-9287</contrib-id><name-alternatives><name xml:lang="en"><surname>Cheremushkin</surname><given-names>Sergey V.</given-names></name><name xml:lang="ru"><surname>Черемушкин</surname><given-names>Сергей Викторович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Cand. Sci. (Med.)</p></bio><bio xml:lang="ru"><p>канд. мед. наук, зам. глав. врача по терапевтической помощи, доц. каф. пропедевтики внутренних болезней и гастроэнтерологии, гл. терапевт</p></bio><email>svch555362@yandex.ru</email><xref ref-type="aff" rid="aff3"/><xref ref-type="aff" rid="aff4"/><xref ref-type="aff" rid="aff5"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Russian Medical Academy of Continuous Professional Education</institution></aff><aff><institution xml:lang="ru">ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">Sechenov First Moscow State Medical University (Sechenov University)</institution></aff><aff><institution xml:lang="ru">ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет)</institution></aff></aff-alternatives><aff-alternatives id="aff3"><aff><institution xml:lang="en">Central Clinical Hospital of the Medicine of the Russian Railways</institution></aff><aff><institution xml:lang="ru">ЧУЗ «Центральная клиническая больница „РЖД-Медицина“»</institution></aff></aff-alternatives><aff-alternatives id="aff4"><aff><institution xml:lang="en">Yevdokimov Moscow State University of Medicine and Dentistry</institution></aff><aff><institution xml:lang="ru">ФГБОУ ВО «Московский государственный медико-стоматологический университет им. А.И. Евдокимова» Минздрава России</institution></aff></aff-alternatives><aff-alternatives id="aff5"><aff><institution xml:lang="en">Central Directorate of Healthcare – branch of Russian Railways</institution></aff><aff><institution xml:lang="ru">Центральная дирекция здравоохранения – филиала ОАО «РЖД»</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2023-05-15" publication-format="electronic"><day>15</day><month>05</month><year>2023</year></pub-date><volume>25</volume><issue>5</issue><issue-title xml:lang="en">Gastroenterology</issue-title><issue-title xml:lang="ru">Гастроэнтерология</issue-title><fpage>368</fpage><lpage>374</lpage><history><date date-type="received" iso-8601-date="2023-07-30"><day>30</day><month>07</month><year>2023</year></date><date date-type="accepted" iso-8601-date="2023-07-30"><day>30</day><month>07</month><year>2023</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2023, Consilium Medicum</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2023, ООО "Консилиум Медикум"</copyright-statement><copyright-year>2023</copyright-year><copyright-holder xml:lang="en">Consilium Medicum</copyright-holder><copyright-holder xml:lang="ru">ООО "Консилиум Медикум"</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by-nc-sa/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://consilium.orscience.ru/2075-1753/article/view/567876">https://consilium.orscience.ru/2075-1753/article/view/567876</self-uri><abstract xml:lang="en"><p>Prevention of thromboembolic complications is the main goal in patients with atrial fibrillation. Anticoagulant therapy is used as prophylaxis, and direct oral anticoagulants are preferred. However, this therapy is associated with a risk of bleeding, among which gastrointestinal bleeding takes a leading place. Proton pump inhibitors are now widely used as prophylaxis for upper gastrointestinal bleedings, but when used long-term, may be associated with a number of adverse drug reactions, including an increased risk of adverse cardiovascular events. Long-term use of these drugs may suppress the action of antiplatelet drugs, disrupt the function of the vascular endothelium, and at the same time cause hypomagnesemia, iron deficiency, vitamin D and K deficiency. At the same time, monotherapy with proton pump inhibitors does not protect against the risk of bleeding from the lower gastrointestinal tract. Thus, as an effective gastro- and enteroprotection, it is necessary to prescribe drugs that protect the gastrointestinal tract throughout its entire length. Such a drug is rebamipide, which has a complex protective effect on the gastrointestinal tract, protecting the mucous membrane at all its levels (pre-, post-epithelial and directly epithelial level), and ensures the restoration of tight contacts in the epithelium of the intestinal tube throughout its entire length. It should be noted that the current consensus documents of the leading experts on the problem of decreasing the risk of gastrointestinal bleedings during direct oral anticoagulant treatment recommend the use of rebamipide for the entire duration of therapy.</p></abstract><trans-abstract xml:lang="ru"><p>Профилактика тромбоэмболических осложнений является главной целью у пациентов с фибрилляцией предсердий. Для этого используют антикоагулянтную терапию, и здесь предпочтение отдается прямым оральным антикоагулянтам. Однако данная терапия сопряжена с риском кровотечений, среди которых желудочно-кишечные кровотечения (ЖКК) занимают лидирующее место. В настоящее время для профилактики ЖКК из верхних отделов желудочно-кишечного тракта (ЖКТ) широко применяются ингибиторы протонной помпы (ИПП), которые, однако, при долгосрочном применении могут ассоциироваться с рядом нежелательных лекарственных реакций, включая повышение риска неблагоприятных сердечно-сосудистых событий. Согласно имеющимся данным длительный прием ИПП может влиять на эффекты антитромбоцитарных препаратов, нарушать функцию эндотелия сосудов, индуцировать гипомагниемию, дефицит железа, витаминов D и К. Одновременно с этим терапия ИПП не защищает от риска кровотечений из нижних отделов ЖКТ. Таким образом, в качестве эффективной гастро- и энтеропротекции необходимо назначать препараты, обеспечивающие защиту ЖКТ на всем его протяжении. Таким препаратом является ребамипид, оказывающий комплексное протективное действие на ЖКТ, защищая слизистую оболочку на всех ее уровнях организации (пре-, постэпителиальном и непосредственно эпителиальном) и обеспечивая восстановление плотных контактов в эпителии пищеварительной трубки на всем ее протяжении. Следует отметить, что в актуальных согласительных документах ведущих экспертов по проблеме снижения риска ЖКК на фоне терапии прямыми оральными антикоагулянтами именно ребамипид рекомендуется к применению на всем ее протяжении.</p></trans-abstract><kwd-group xml:lang="en"><kwd>atrial fibrillation</kwd><kwd>direct oral anticoagulants</kwd><kwd>vitamin K antagonists</kwd><kwd>gastroprotective therapy</kwd><kwd>gastrointestinal bleeding</kwd><kwd>proton-pump inhibitors</kwd><kwd>rebamipide</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>фибрилляция предсердий</kwd><kwd>прямые оральные антикоагулянты</kwd><kwd>антагонисты витамина K</kwd><kwd>гастропротективная терапия</kwd><kwd>желудочно-кишечные кровотечения</kwd><kwd>ингибиторы протонной помпы</kwd><kwd>ребамипид</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Bassand JP, Apenteng PN, Atar D, et al. GARFIELD-AF: a worldwide prospective registry of patients with atrial fibrillation at risk of stroke. Future Cardiol. 2021;17(1):19-38.</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Dai H, Zhang Q, Much AA, et al. Global, regional, and national prevalence, incidence, mortality, and risk factors for atrial fibrillation, 1990–2017: results from the Global Burden of Disease Study 2017. Eur Heart J Qual Care Clin Outcomes. 2021;7(6):574-82.</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Аракелян М.Г., Бокерия Л.А., Васильева Е.Ю., и др. Фибрилляция и трепетание предсердий. Клинические рекомендации 2020. Российский кардиологический журнал. 2021;26(7):4594 [Arakelyan MG, Bockeria LA, Vasilieva EYu, et al. 2020 Clinical guidelines for Atrial fibrillation and atrial flutter. Russian Journal of Cardiology. 2021;26(7):4594 (in Russian)].</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Schwarb H, Tsakiris DA. New Direct Oral Anticoagulants (DOAC) and Their Use Today. Dent J (Basel). 2016;4(1):5.</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2019;74(1):104-32.</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Cheung KS, Leung WK. Gastrointestinal bleeding in patients on novel oral anticoagulants: Risk, prevention and management. World J Gastroenterol. 2017;23(11):1954-63.</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Xu Y, Schulman S, Dowlatshahi D, et al. Direct Oral Anticoagulant- or Warfarin-Related Major Bleeding: Characteristics, Reversal Strategies, and Outcomes From a Multicenter Observational Study. Chest. 2017;152(1):81-91.</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Green L, Tan J, Morris JK, et al. A three-year prospective study of the presentation and clinical outcomes of major bleeding episodes associated with oral anticoagulant use in the UK (ORANGE study). Haematologica. 2018;103(4):738-45.</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Bahit MC, Lopes RD, Wojdyla DM, et al. Non-major bleeding with apixaban versus warfarin in patients with atrial fibrillation. Heart. 2017;103(8):623-8.</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Xu Y, Siegal DM. Anticoagulant-associated gastrointestinal bleeding: Framework for decisions about whether, when and how to resume anticoagulants. J Thromb Haemost. 2021;19(10):2383-93.</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Gomes T, Mamdani MM, Holbrook AM, et al. Rates of hemorrhage during warfarin therapy for atrial fibrillation. CMAJ. 2013;185(2):E121-7.</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Bouget J, Viglino D, Yvetot Q, et al. Major gastrointestinal bleeding and antithrombotics: Characteristics and management. World J Gastroenterol. 2020;26(36):5463-73.</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Raymond J, Imbert L, Cousin T, et al. Pharmacogenetics of Direct Oral Anticoagulants: A Systematic Review. J Pers Med. 2021;11(1):37.</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Thapa N, Shatzel J, Deloughery TG, et al. Direct oral anticoagulants in gastrointestinal malignancies: is the convenience worth the risk? J Gastrointest Oncol. 2019;10(4):807-9.</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Desai J, Granger CB, Weitz JI, et al. Novel oral anticoagulants in gastroenterology practice. Gastrointest Endosc. 2013;78(2):227-39.</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Hellenbart EL, Faulkenberg KD, Finks SW. Evaluation of bleeding in patients receiving direct oral anticoagulants. Vasc Health Risk Manag. 2017;13:325-42.</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Lim YJ, Yang CH. Non-steroidal anti-inflammatory drug-induced enteropathy. Clin Endosc. 2012;45(2):138-44.</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>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(21):2363-72.</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>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(2):386-99.</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>White EM, Coons JC. Direct Oral Anticoagulant Use in Special Populations: Elderly, Obesity, and Renal Failure. Curr Cardiol Rep. 2021;23(4):27.</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Gunasekaran K, Rajasurya V, Devasahayam J, et al. A Review of the Incidence Diagnosis and Treatment of Spontaneous Hemorrhage in Patients Treated with Direct Oral Anticoagulants. J Clin Med. 2020;9(9):2984.</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Soliman EZ, Prineas RJ, Go AS, et al. Chronic kidney disease and prevalent atrial fibrillation: the Chronic Renal Insufficiency Cohort (CRIC). Am Heart J. 2010;159(6):1102-7.</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Padrini R. Clinical pharmacokinetics and pharmacodynamics of direct oral anticoagulants in patients with renal failure. Eur J Drug Metab Pharmacokinet. 2019;44(1):1-12.</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>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;23(10):1612-76.</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Lobraico-Fernandez J, Baksh S, Nemec E. Elderly Bleeding Risk of Direct Oral Anticoagulants in Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-Analysis of Cohort Studies. Drugs R D. 2019;19(3):235-45.</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Abraham NS, Noseworthy PA, Yao X, et al. Gastrointestinal Safety of Direct Oral Anticoagulants: A Large Population-Based Study. Gastroenterology. 2017;152(5):1014-22.e1.</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Schaefer JK, Errickson J, Li Y, et al. Adverse Events Associated With the Addition of Aspirin to Direct Oral Anticoagulant Therapy Without a Clear Indication. JAMA Intern Med. 2021;181(6):817-24.</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Penner LS, Gavan SP, Ashcroft DM, et al. Does coprescribing nonsteroidal anti-inflammatory drugs and oral anticoagulants increase the risk of major bleeding, stroke and systemic embolism? Br J Clin Pharmacol. 2022;88(11):4789-811.</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the Management of Atrial Fibrillation Developed in Collaboration With EACTS. Rev Esp Cardiol (Engl Ed). 2017;70(1):50.</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Steffel J, Verhamme P, Potpara TS, 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. Eur Heart J. 2018;39(16):1330-93.</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Gong IY, Kim RB. Importance of pharmacokinetic profile and variability as determinants of dose and response to dabigatran, rivaroxaban, and apixaban. Can J Cardiol. 2013;29(7 Suppl.):S24-33.</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Alexander JH, Lopes RD, James S, et al. Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med. 2011;365(8):699-708.</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Консенсус экспертов по снижению риска желудочно-кишечных кровотечений у пациентов, получающих оральные антикоагулянты. Терапия. 2021;10:23-41 [Experts consensus on reducing the risk of gastrointestinal bleeding in patients receiving oral anticoagulants. Therapy. 2021;10:23-41 (in Russian)].</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Остроумова О.Д., Орлова И.Ю., Кочетков А.И., и др. Структура сопутствующих заболеваний органов пищеварения у пациентов, получающих прямые оральные антикоагулянты: результаты многоцентрового кросс-секционного фармакоэпидемиологического исследования. Терапия. 2022;8(10):152-61 [Ostroumova OD, Orlova IY, Kochetkov AI, et al. Structure of polymorbidities of the digestive diseases in patients receiving direct oral anticoagulants: results of a multicenter cross-sectional pharmacoepidemiological study. Therapy. 2022;8(10):152-61 (in Russian)].</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>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.</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>Barkun AN, Laine L, Leontiadis GI, et al. Management of Nonvariceal Upper Gastrointestinal Bleeding. Ann Intern Med. 2020;172(8):573.</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>Ray WA, Chung CP, Murray KT, et al. Association of Oral Anticoagulants and Proton Pump Inhibitor Cotherapy With Hospitalization for Upper Gastrointestinal Tract Bleeding. JAMA. 2018;320(21):2221-30.</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>Vaezi MF, Yang YX, Howden CW. Complications of Proton Pump Inhibitor Therapy. Gastroenterology. 2017;153(1):35-48.</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>Khan M, Santana J, Donnellan C, et al. Medical treatments in the short term management of reflux oesophagitis. Cochrane Database Syst Rev. 2007;2:CD003244.</mixed-citation></ref><ref id="B40"><label>40.</label><mixed-citation>Laheij RJ, Sturkenboom MC, Hassing RJ, et al. Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs. JAMA. 2004;292(16):1955-60.</mixed-citation></ref><ref id="B41"><label>41.</label><mixed-citation>Yang YX, Lewis JD, Epstein S, et al. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296(24):2947-53.</mixed-citation></ref><ref id="B42"><label>42.</label><mixed-citation>Neal KR, Scott HM, Slack RC, Logan RF. Omeprazole as a risk factor for campylobacter gastroenteritis: case-control study. BMJ. 1996;312(7028):414-5.</mixed-citation></ref><ref id="B43"><label>43.</label><mixed-citation>Lazarus B, Chen Y, Wilson FP, et al. Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease. JAMA Intern Med. 2016;176(2):238-46.</mixed-citation></ref><ref id="B44"><label>44.</label><mixed-citation>Gomm W, von Holt K, Thomé F, et al. Association of Proton Pump Inhibitors With Risk of Dementia: A Pharmacoepidemiological Claims Data Analysis. JAMA Neurol. 2016;73(4):410-6.</mixed-citation></ref><ref id="B45"><label>45.</label><mixed-citation>Cheung KS, Chan EW, Wong AYS, et al. Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study. Gut. 2018;67(1):28-35.</mixed-citation></ref><ref id="B46"><label>46.</label><mixed-citation>Xie Y, Bowe B, Li T, et al. Risk of death among users of Proton Pump Inhibitors: a longitudinal observational cohort study of United States veterans. BMJ Open. 2017;7(6):e015735.</mixed-citation></ref><ref id="B47"><label>47.</label><mixed-citation>Simonov M, Abel EE, Skanderson M, et al. Use of Proton Pump Inhibitors Increases Risk of Incident Kidney Stones. Clin Gastroenterol Hepatol. 2021;19(1):72-9.e21.</mixed-citation></ref><ref id="B48"><label>48.</label><mixed-citation>Almario CV, Chey WD, Spiegel BMR. Increased Risk of COVID-19 Among Users of Proton Pump Inhibitors. Am J Gastroenterol. 2020;115(10):1707-15.</mixed-citation></ref><ref id="B49"><label>49.</label><mixed-citation>Hu W, Luo Y, Yang X. Inappropriate Use of Proton Pump Inhibitors Increases Cardiovascular Events in Patients with Coronary Heart Disease. Int J Gen Med. 2022;15:8685-91.</mixed-citation></ref><ref id="B50"><label>50.</label><mixed-citation>Charlot M, Grove EL, Hansen PR, et al. Proton pump inhibitor use and risk of adverse cardiovascular events in aspirin treated patients with first time myocardial infarction: nationwide propensity score matched study. BMJ. 2011;342:d2690.</mixed-citation></ref><ref id="B51"><label>51.</label><mixed-citation>Würtz M, Grove EL, Kristensen SD, Hvas AM. The antiplatelet effect of aspirin is reduced by proton pump inhibitors in patients with coronary artery disease. Heart. 2010;96(5):368-71.</mixed-citation></ref><ref id="B52"><label>52.</label><mixed-citation>Hu W, Tong J, Kuang X, et al. Influence of proton pump inhibitors on clinical outcomes in coronary heart disease patients receiving aspirin and clopidogrel: A meta-analysis. Medicine (Baltimore). 2018;97(3):e9638.</mixed-citation></ref><ref id="B53"><label>53.</label><mixed-citation>Hagymási K, Müllner K, Herszényi L, Tulassay Z. Update on the pharmacogenomics of proton pump inhibitors. Pharmacogenomics. 2011;12(6):873-88.</mixed-citation></ref><ref id="B54"><label>54.</label><mixed-citation>Weisz G, Smilowitz NR, Kirtane AJ, et al. Proton Pump Inhibitors, Platelet Reactivity, and Cardiovascular Outcomes After Drug-Eluting Stents in Clopidogrel-Treated Patients: The ADAPT-DES Study. Circ Cardiovasc Interv. 2015;8(10):e001952.</mixed-citation></ref><ref id="B55"><label>55.</label><mixed-citation>Ben Ghezala I, Luu M, Bardou M. An update on drug-drug interactions associated with proton pump inhibitors. Expert Opin Drug Metab Toxicol. 2022;18(5):337-46.</mixed-citation></ref><ref id="B56"><label>56.</label><mixed-citation>Lim IH, Lee SJ, Shin BS, Kang HG. Ilaprazole and Clopidogrel Resistance in Acute Stroke Patients. Biomedicines. 2022;10(6):1366.</mixed-citation></ref><ref id="B57"><label>57.</label><mixed-citation>Hamano H, Niimura T, Horinouchi Y, et al. Proton pump inhibitors block iron absorption through direct regulation of hepcidin via the aryl hydrocarbon receptor-mediated pathway. Toxicol Lett. 2020;318:86-91.</mixed-citation></ref><ref id="B58"><label>58.</label><mixed-citation>Yepuri G, Sukhovershin R, Nazari-Shafti TZ, et al. Proton Pump Inhibitors Accelerate Endothelial Senescence. Circ Res. 2016;118(12):e36-42.</mixed-citation></ref><ref id="B59"><label>59.</label><mixed-citation>Taneja G, Thanikachalam PV, Rajput SK. Dose and time-dependent toxicological impact of pantoprazole on vascular endothelium and renal tissue. Toxicol Lett. 2020;333:97-104.</mixed-citation></ref><ref id="B60"><label>60.</label><mixed-citation>Kamiya C, Odagiri K, Hakamata A, et al. Omeprazole suppresses endothelial calcium response and eNOS Ser1177 phosphorylation in porcine aortic endothelial cells. Mol Biol Rep. 2021;48(7):5503-11.</mixed-citation></ref><ref id="B61"><label>61.</label><mixed-citation>Suksridechacin N, Kulwong P, Chamniansawat S, Thongon N. Effect of prolonged omeprazole administration on segmental intestinal Mg2+ absorption in male Sprague-Dawley rats. World J Gastroenterol. 2020;26(11):1142-55.</mixed-citation></ref><ref id="B62"><label>62.</label><mixed-citation>Danziger J, William JH, Scott DJ, et al. Proton-pump inhibitor use is associated with low serum magnesium concentrations. Kidney Int. 2013;83(4):692-9.</mixed-citation></ref><ref id="B63"><label>63.</label><mixed-citation>Douwes RM, Gomes-Neto AW, Schutten JC, et al. Proton-Pump Inhibitors and Hypomagnesaemia in Kidney Transplant Recipients. J Clin Med. 2019;8(12):2162.</mixed-citation></ref><ref id="B64"><label>64.</label><mixed-citation>Kieboom BC, Kiefte-de Jong JC, Eijgelsheim M, et al. Proton pump inhibitors and hypomagnesemia in the general population: a population-based cohort study. Am J Kidney Dis. 2015;66(5):775-82.</mixed-citation></ref><ref id="B65"><label>65.</label><mixed-citation>Sutton SS, Magagnoli J, Cummings T, Hardin JW. The Association between the Use of Proton Pump Inhibitors and the Risk of Hypomagnesemia in a National Cohort of Veteran Patients with HIV. J Int Assoc Provid AIDS Care. 2019;18:2325958218821652.</mixed-citation></ref><ref id="B66"><label>66.</label><mixed-citation>Gommers LMM, Hoenderop JGJ, de Baaij JHF. Mechanisms of proton pump inhibitor-induced hypomagnesemia. Acta Physiol (Oxf). 2022;235(4):e13846.</mixed-citation></ref><ref id="B67"><label>67.</label><mixed-citation>Flink EB. Magnesium deficiency. Etiology and clinical spectrum. Acta Med Scand Suppl. 1981;647:125-37.</mixed-citation></ref><ref id="B68"><label>68.</label><mixed-citation>Fatemi S, Ryzen E, Flores J, et al. Effect of experimental human magnesium depletion on parathyroid hormone secretion and 1,25-dihydroxyvitamin D metabolism. J Clin Endocrinol Metab. 1991;73(5):1067-72.</mixed-citation></ref><ref id="B69"><label>69.</label><mixed-citation>Freitag JJ, Martin KJ, Conrades MB, et al. Evidence for skeletal resistance to parathyroid hormone in magnesium deficiency. Studies in isolated perfused bone. J Clin Invest. 1979;64(5):1238-44.</mixed-citation></ref><ref id="B70"><label>70.</label><mixed-citation>al-Ghamdi SM, Cameron EC, Sutton RA. Magnesium deficiency: pathophysiologic and clinical overview. Am J Kidney Dis. 1994;24(5):737-52.</mixed-citation></ref><ref id="B71"><label>71.</label><mixed-citation>Srinutta T, Chewcharat A, Takkavatakarn K, et al. Proton pump inhibitors and hypomagnesemia: A meta-analysis of observational studies. Medicine (Baltimore). 2019;98(44):e17788.</mixed-citation></ref><ref id="B72"><label>72.</label><mixed-citation>Hess MW, Hoenderop JG, Bindels RJ, Drenth JP. Systematic review: hypomagnesaemia induced by proton pump inhibition. Aliment Pharmacol Ther. 2012;36(5):405-13.</mixed-citation></ref><ref id="B73"><label>73.</label><mixed-citation>de Baaij JH, Hoenderop JG, Bindels RJ. Magnesium in man: implications for health and disease. Physiol Rev. 2015;95(1):1-46.</mixed-citation></ref><ref id="B74"><label>74.</label><mixed-citation>Lam JR, Schneider JL, Quesenberry CP, Corley DA. Proton Pump Inhibitor and Histamine-2 Receptor Antagonist Use and Iron Deficiency. Gastroenterology. 2017;152(4):821-29.e1.</mixed-citation></ref><ref id="B75"><label>75.</label><mixed-citation>Meng H, Wang Y, Ruan J, et al. Decreased Iron Ion Concentrations in the Peripheral Blood Correlate with Coronary Atherosclerosis. Nutrients. 2022;14(2):319.</mixed-citation></ref><ref id="B76"><label>76.</label><mixed-citation>Bruno G, Zaccari P, Rocco G, et al. Proton pump inhibitors and dysbiosis: Current knowledge and aspects to be clarified. World J Gastroenterol. 2019;25(22):2706-19.</mixed-citation></ref><ref id="B77"><label>77.</label><mixed-citation>Scarpignato C, Bjarnason I. Drug-Induced Small Bowel Injury: a Challenging and Often Forgotten Clinical Condition. Curr Gastroenterol Rep. 2019;21(11):55.</mixed-citation></ref><ref id="B78"><label>78.</label><mixed-citation>Janus SE, Durieux JC, Hajjari J, et al. Inflammation-mediated vitamin K and vitamin D effects on vascular calcifications in people with HIV on active antiretroviral therapy. AIDS. 20221;36(5):647-55.</mixed-citation></ref><ref id="B79"><label>79.</label><mixed-citation>Xu C, Cunqing Y, Chun G, et al. The relationship between serum vitamin K concentration and coronary artery calcification in middle-aged and elderly people. Clin Chim Acta. 2022;531:325-30.</mixed-citation></ref><ref id="B80"><label>80.</label><mixed-citation>Kunadian V, Ford GA, Bawamia B, et al. Vitamin D deficiency and coronary artery disease: a review of the evidence. Am Heart J. 2014;167(3):283-91.</mixed-citation></ref><ref id="B81"><label>81.</label><mixed-citation>Verdoia M, Viglione F, Boggio A, et al. Vitamin D deficiency is associated with impaired reperfusion in STEMI patients undergoing primary percutaneous coronary intervention. Vascul Pharmacol. 2021;140:106897.</mixed-citation></ref><ref id="B82"><label>82.</label><mixed-citation>Watanabe T, 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.</mixed-citation></ref><ref id="B83"><label>83.</label><mixed-citation>Pittayanon R, Piyachaturawat P, Rerknimitr R, et al. Cytoprotective agent for peptic ulcer prevention in patients taking dual antiplatelet agents: A randomized, double-blind placebo-controlled trial. J Gastroenterol Hepatol. 2019;34(9):1517-22.</mixed-citation></ref><ref id="B84"><label>84.</label><mixed-citation>Yamashita T, Watanabe E, Ikeda T, et al. Observational study of the effects of dabigatran on gastrointestinal symptoms in patients with non-valvular atrial fibrillation. J Arrhythm. 2014;30(6):478-84.</mixed-citation></ref><ref id="B85"><label>85.</label><mixed-citation>Остроумова О.Д., Кочетков А.И. Роль нарушений структуры кишечного барьера в патогенезе сердечно-сосудистых заболеваний и возможности ребамипида в их коррекции. Фарматека. 2020;3:29-41 [Ostroumova OD, Kochetkov AI. The role of the disturbances in the intestinal barrier structure in relation to cardiovascular diseases pathogenesis and rebamipid potential in their correction. Farmateka. 2020;13:29-41 (in Russian)].</mixed-citation></ref><ref id="B86"><label>86.</label><mixed-citation>Симаненков В.И., Маев И.В., Ткачева О.Н., и др. Синдром повышенной эпителиальной проницаемости в клинической практике. Мультидисциплинарный национальный консенсус. Кардиоваскулярная терапия и профилактика. 2021;20(1):2758 [Simanenkov VI, Maev IV, Tkacheva ON, et al. Syndrome of increased epithelial permeability in clinical practice. Multidisciplinary national Consensus. Cardiovascular Therapy and Prevention. 2021;20(1):2758 (in Russian)].</mixed-citation></ref><ref id="B87"><label>87.</label><mixed-citation>Naito Y, Yoshikawa T. Rebamipide: a gastrointestinal protective drug with pleiotropic activities. Expert Rev Gastroenterol Hepatol. 2010;4(3):261-70.</mixed-citation></ref><ref id="B88"><label>88.</label><mixed-citation>Tanigawa T, Watanabe T, Higashimori A, et al. Rebamipide ameliorates indomethacin-induced small intestinal damage and proton pump inhibitor-induced exacerbation of this damage by modulation of small intestinal microbiota. PLoS One. 2021;16(1):e0245995.</mixed-citation></ref><ref id="B89"><label>89.</label><mixed-citation>Lee MY, Lee S, Heo KN, et al. Rebamipide as a Potential Alternative Gastroprotective Agent to Proton Pump Inhibitor in Elderly Chronic Nonsteroidal Anti-Inflammatory Drug Users without Risk Factors. Int J Gen Med. 2022;15:2835-45.</mixed-citation></ref><ref id="B90"><label>90.</label><mixed-citation>Imai T, Hazama K, Kosuge Y, et al. Preventive effect of rebamipide on NSAID-induced lower gastrointestinal tract injury using FAERS and JADER. Sci Rep. 2022;12(1):2631.</mixed-citation></ref><ref id="B91"><label>91.</label><mixed-citation>Maiden L, Thjodleifsson B, Theodors A, et al. A quantitative analysis of NSAID-induced small bowel pathology by capsule enteroscopy. Gastroenterology. 2005;128(5):1172-8.</mixed-citation></ref><ref id="B92"><label>92.</label><mixed-citation>Tsujimoto H, Hirata Y, Ueda Y, et al. Effect of a proton-pump inhibitor on intestinal microbiota in patients taking low-dose aspirin. Eur J Clin Pharmacol. 2021;77(11):1639-48.</mixed-citation></ref><ref id="B93"><label>93.</label><mixed-citation>Takashima S, Tanaka F, Kawaguchi Y, et al. Proton pump inhibitors enhance intestinal permeability via dysbiosis of gut microbiota under stressed conditions in mice. Neurogastroenterol Motil. 2020;32(7):e13841.</mixed-citation></ref><ref id="B94"><label>94.</label><mixed-citation>Zhu B, Zhang W, Lu Y, et al. Network pharmacology-based identification of protective mechanism of Panax Notoginseng Saponins on aspirin induced gastrointestinal injury. Biomed Pharmacother. 2018;105:159-66.</mixed-citation></ref><ref id="B95"><label>95.</label><mixed-citation>Arakawa T, Higuchi K, Fujiwara Y, et al. 15th anniversary of rebamipide: looking ahead to the new mechanisms and new applications. Dig Dis Sci. 2005;50 Suppl. 1:S3-S11.</mixed-citation></ref><ref id="B96"><label>96.</label><mixed-citation>Zhang WT, Wang MR, Hua GD, et al. Inhibition of Aspirin-Induced Gastrointestinal Injury: Systematic Review and Network Meta-Analysis. Front Pharmacol. 2021;12:730681.</mixed-citation></ref></ref-list></back></article>
