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Кардиоваскулярный риск при длительном применении ингибиторов протонной помпы: миф или реальность
Кардиоваскулярный риск при длительном применении ингибиторов протонной помпы: миф или реальность
Трухан Д.И., Филимонов С.Н. Кардиоваскулярный риск при длительном применении ингибиторов протонной помпы: миф или реальность. Consilium Medicum. 2024;26(1):55–60.
DOI: 10.26442/20751753.2024.1.202532
© ООО «КОНСИЛИУМ МЕДИКУМ», 2024 г.
DOI: 10.26442/20751753.2024.1.202532
© ООО «КОНСИЛИУМ МЕДИКУМ», 2024 г.
________________________________________________
Материалы доступны только для специалистов сферы здравоохранения. Авторизуйтесь или зарегистрируйтесь.
Аннотация
Ингибиторы протонной помпы (ИПП) являются наиболее эффективными препаратами для лечения кислотозависимых заболеваний. В последние десятилетия использование ИПП растет в геометрической прогрессии. Из гастроэнтерологической практики ИПП активно внедряются и в другие специальности, в частности в кардиологию и ревматологию, где применяются с целью защиты слизистой оболочки желудочно-кишечного тракта и предупреждения желудочно-кишечных кровотечений при долгосрочной антитромботической терапии и длительном применении нестероидных противовоспалительных препаратов. Долгое время ИПП считались полностью безопасными лекарственными веществами как для краткосрочного, так и для длительного применения. Однако в современных клинических рекомендациях отмечается, что при назначении ИПП в больших дозах на длительный срок следует учитывать возможность развития побочных эффектов. В последние годы опубликован ряд зарубежных обзоров, в которых рассматриваются связи между ИПП и рядом заболеваний/состояний, где в том числе затрагивается вопрос о возможной ассоциации приема ИПП с повышенным риском сердечно-сосудистых осложнений, но при этом отмечается противоречивость этих данных. В информационных базах PubMed и Scopus мы провели поиск публикаций, посвященных безопасности применения ИПП, включавший источники до 01.12.2023. В рамках обзора мы рассмотрели возможный кардиоваскулярный риск длительного применения ИПП. Анализ публикаций, несмотря на ряд противоречий, позволяет сделать вывод, что кардиоваскулярный риск при длительном применении ИПП реален и его необходимо учитывать при назначении ИПП на длительный срок и коморбидным/мультиморбидным пациентам.
Ключевые слова: ингибиторы протонной помпы, лекарственная безопасность, побочные эффекты, сердечно-сосудистый риск, неблагоприятные сердечно-сосудистые события, инфаркт миокарда, инсульт, сахарный диабет, хроническая болезнь почек, рабдомиолиз
Keywords: proton pump inhibitors, drug safety, side effects, cardiovascular risk, adverse cardiovascular events, myocardial infarction, stroke, diabetes mellitus, chronic kidney disease, rhabdomyolysis
Ключевые слова: ингибиторы протонной помпы, лекарственная безопасность, побочные эффекты, сердечно-сосудистый риск, неблагоприятные сердечно-сосудистые события, инфаркт миокарда, инсульт, сахарный диабет, хроническая болезнь почек, рабдомиолиз
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Keywords: proton pump inhibitors, drug safety, side effects, cardiovascular risk, adverse cardiovascular events, myocardial infarction, stroke, diabetes mellitus, chronic kidney disease, rhabdomyolysis
Полный текст
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3. Chislo umershikh po prichinam smerti v 2021 godu. Rosstat. Available at: https://view.officeapps.live.com/op/view.aspx?src=https%3A%2F%2Frosstat.gov.ru%2Fstorage%2Fmediabank.... Accessed: 12.12.2023 (in Russian).
4. Tarasova LV, Trukhan DI. Drug safety in gastroenterology. Experimental and Clinical Gastroenterology. 2013;4:81-7 (in Russian).
5. Trukhan DI. Rational pharmacotherapy in real clinical practice through the prism of multimorbidity and drug safety. Clinical Review for General Practice. 2020;2:29-39 (in Russian). DOI:10.47407/kr2020.1.2.00015
6. Trukhan DI, Konshu NV. Rational pharmacotherapy in the clinic of internal diseases through the prism of multimorbidity and drug safety. Handbook for Practitioners Doctors. 2019;2:10-8 (in Russian).
7. Ivashkin VT, Maev IV, Trukhmanov AS, et al. Recommendations of the Russian Gastroenterological Association in Diagnosis and Treatment of Gastroesophageal Reflux Disease. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2020;30(4):70-97 (in Russian). DOI:10.22416/1382-4376-2020-30-4-70-97
8. Al-Aly Z, Maddukuri G, Xie Y. Proton pump inhibitors and the kidney: implications of current evidence for clinical practice and when and how to deprescribe. Am J Kidney Dis. 2020;75(4):497-507. DOI:10.1053/j.ajkd.2019.07.012
9. Novotny M, Klimova B, Valis M. PPI Long Term Use: Risk of Neurological Adverse Events? Front Neurol. 2019;9:1142. DOI:10.3389/fneur.2018.01142
10. Salvo EM, Ferko NC, Cash SB, et al. Umbrella review of 42 systematic reviews with meta-analyses: the safety of proton pump inhibitors. Aliment Pharmacol Ther. 2021;54(2):129-43. DOI:10.1111/apt.16407
11. Chinzon D, Domingues G, Tosetto N, Perrotti M. Safety of long-term proton pump inhibitors: facts and myths. Arq Gastroenterol. 2022;59(2):219-25.
DOI:10.1590/S0004-2803.202202000-40
12. Maideen NMP. Adverse Effects Associated with Long-Term Use of Proton Pump Inhibitors. Chonnam Med J. 2023;59(2):115-27. DOI:10.4068/cmj.2023.59.2.115
13. Smith CA, Ebrahimpour A, Novikova L, et al. Esomeprazole covalently interacts with the cardiovascular enzyme dimethylarginine dimethylaminohydrolase: Insights into the cardiovascular risk of proton pump inhibitors. Biochim Biophys Acta Gen Subj. 2022;1866(8):130149. DOI:10.1016/j.bbagen.2022.130149
14. Ariel H, Cooke JP. Cardiovascular risk of proton pump inhibitors. Methodist Debakey Cardiovasc J. 2019;15(3):214-9. DOI:10.14797/mdcj-15-3-214
15. Koyyada A. Long-term use of proton pump inhibitors as a risk factor for various adverse manifestations. Therapie. 2021;76(1):13-21. DOI:10.1016/j.therap.2020.06.019
16. Nochaiwong S, Ruengorn C, Awiphan R, et al. The association between proton pump inhibitor use and the risk of adverse kidney outcomes: a systematic review and meta-analysis. Nephrol Dial Transplant. 2018;33(2):331-42. DOI:10.1093/ndt/gfw470
17. Rooney MR, Bell EJ, Alonso A, et al. Proton Pump Inhibitor Use, Hypomagnesemia and Risk of Cardiovascular Diseases: The Atherosclerosis Risk in Communities (ARIC) Study. J Clin Gastroenterol. 2021;55(8):677-83. DOI:10.1097/MCG.0000000000001420
18. Sun S, Cui Z, Zhou M, et al. Proton pump inhibitor monotherapy and the risk of cardiovascular events in patients with gastro-esophageal reflux disease: a meta-analysis. Neurogastroenterol Motil. 2017;29(2):e12926. DOI:10.1111/nmo.12926
19. Bundhun PK, Teeluck AR, Bhurtu A, Huang WQ. Is the concomitant use of clopidogrel and Proton Pump Inhibitors still associated with increased adverse cardiovascular outcomes following coronary angioplasty?: a systematic review and meta-analysis of recently published studies (2012–2016). BMC Cardiovasc Disord. 2017;17(1):3.
DOI:10.1186/s12872-016-0453-6
20. Pang J, Wu Q, Zhang Z, et al. Efficacy and safety of clopidogrel only vs. clopidogrel added proton pump inhibitors in the treatment of patients with coronary heart disease after percutaneous coronary intervention: A systematic review and meta-analysis. Int J Cardiol Heart Vasc. 2019;23:100317. DOI:10.1016/j.ijcha.2018.12.016
21. Freedberg DE, Yang YX, Abrams JA. Proton pump inhibitors and myocardial infarction. Gastroenterology. 2015;149(4):830-3. DOI:10.1053/j.gastro.2015.08.002
22. Tseng HJ, Cheng CM, Tsai SJ, et al. Proton pump inhibitor exposure and acute myocardial infarction risk: a nested cohort study. Cardiovasc Toxicol. 2021;21(6):444-50. DOI:10.1007/s12012-021-09637-2
23. Qian Y, Jick S. Proton-pump inhibitor use and myocardial infarction: a nested case-control study in the UK Clinical Practice Research Datalink. Epidemiology.
2020;31(3):423-31. DOI:10.1097/EDE.0000000000001152
24. Ghebremariam YT, LePendu P, Lee JC, et al. Unexpected effect of proton pump inhibitors: elevation of the cardiovascular risk factor asymmetric dimethylarginine. Circulation. 2013;128(8):845-53. DOI:10.1161/CIRCULATIONAHA.113.003602
25. Kang MK, Shin JH, Kim TJ, et al. Use of proton pump inhibitor may be associated with progression of cerebral small vessel disease. PLoS One. 2022;17(12):e0279257. DOI:10.1371/journal.pone.0279257
26. Sehested TSG, Gerds TA, Fosbøl EL, et al. Long-term use of proton pump inhibitors, dose-response relationship and associated risk of ischemic stroke and myocardial infarction. J Intern Med. 2018;283(3):268-81. DOI:10.1111/joim.12698
27. Wang YF, Chen YT, Luo JC, et al. Proton-pump inhibitor use and the risk of first-time ischemic stroke in the general population: a nationwide population-based study. Am J Gastroenterol. 2017;112(7):1084-93. DOI:10.1038/ajg.2017.101
28. Yang M, He Q, Gao F, et al. Regular use of proton-pump inhibitors and risk of stroke: a population-based cohort study and meta-analysis of randomized-controlled trials. BMC Med. 2021;19(1):316. DOI:10.1186/s12916-021-02180-5
29. Li S, Liu F, Chen C, et al. Real-world relationship between proton pump inhibitors and cerebro-cardiovascular outcomes independent of clopidogrel. Int Heart J.
2019;60(4):910-8. DOI:10.1536/ihj.18-584
30. Farhat N, Fortin Y, Haddad N, et al. Systematic review and meta-analysis of adverse cardiovascular events associated with proton pump inhibitors used alone or in combination with antiplatelet agents. Crit Rev Toxicol. 2019;49(3):215-61. DOI:10.1080/10408444.2019.1583167
31. Nolde M, Ahn N, Dreischulte T, et al. The long-term risk for myocardial infarction or stroke after proton pump inhibitor therapy (2008–2018). Aliment Pharmacol Ther. 2021;54(8):1033-40. DOI:10.1111/apt.16565
32. Shang YS, Zhong PY, Ma Y, et al. Efficacy and safety of proton pump inhibitors in patients with coronary artery diseases receiving oral antiplatelet agents and/or anticoagulants: A systematic review and meta-analysis. J Cardiovasc Pharmacol. 2022;80(1):1-12. DOI:10.1097/FJC.0000000000001284
33. Nolde M, Ahn N, Dreischulte T, et al. Proton pump inhibitors and the risk of cardiovascular events and cardiovascular mortality: a systematic review and meta-analysis of observational studies. Eur J Intern Med. 2022;106:80-9. DOI:10.1016/j.ejim.2022.09.021
34. Chui CSL, Cheung KS, Brown JP, et al. Proton pump inhibitors and myocardial infarction: an application of active comparators in a self-controlled case series. Int J Epidemiol. 2023;52(3):899-907. DOI:10.1093/ije/dyac196
35. Yuan J, He Q, Nguyen LH, et al. Regular use of proton pump inhibitors and risk of type 2 diabetes: results from three prospective cohort studies. Gut.
2021;70(6):1070-7. DOI:10.1136/gutjnl-2020-322557
36. Czarniak P, Ahmadizar F, Hughes J, et al. Proton pump inhibitors are associated with incident type 2 diabetes mellitus in a prospective population-based cohort study. Br J Clin Pharmacol. 2022;88(6):2718-26. DOI:10.1111/bcp.15182
37. Ciardullo S, Rea F, Savaré L, et al. Prolonged Use of Proton Pump Inhibitors and Risk of Type 2 Diabetes: Results From a Large Population-Based Nested Case-Control Study. J Clin Endocrinol Metab. 2022;107(7):e2671-9. DOI:10.1210/clinem/dgac231
38. Guo YR, Liu XM, Wang GX. Exposure to proton pump inhibitors and risk of diabetes: A systematic review and meta-analysis. World J Diabetes. 2023;14(2):120-9. DOI:10.4239/wjd.v14.i2.120
39. Schiffl H, Al-Nemnem E, Lang SM. Proton-pump inhibitors and chronic kidney disease: hidden consequences of an inappropriate drug use? Saudi J Kidney Dis Transpl. 2020;31(2):312-9. DOI:10.4103/1319-2442.284005
40. Arora P, Gupta A, Golzy M, et al. Proton pump inhibitors are associated with increased risk of development of chronic kidney disease. BMC Nephrol. 2016;17(1):112. DOI:10.1186/s12882-016-0325-4
41. 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. DOI:10.1001/jamainternmed.2015.7193
42. Xie Y, Bowe B, Li T, et al. Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury. Kidney Int.
2017;91(6):1482-94. DOI:10.1016/j.kint.2016.12.021
43. Yang H, Juang SY, Liao KF. Proton pump inhibitors use and risk of chronic kidney disease in diabetic patients. Diabetes Res Clin Pract. 2019;147:67-75. DOI:10.1016/j.diabres.2018.11.019
44. Hart E, Dunn TE, Feuerstein S, Jacobs DM. Proton Pump Inhibitors and Risk of Acute and Chronic Kidney Disease: A Retrospective Cohort Study. Pharmacotherapy.
2019;39(4):443-53. DOI:10.1002/phar.2235
45. Rodríguez-Poncelas A, Barceló MA, Saez M, Coll-de-Tuero G. Duration and dosing of proton pump inhibitors associated with high incidence of chronic kidney disease in population-based cohort. PLoS One. 2018;13(10):e0204231. DOI:10.1371/journal.pone.0204231
46. Guedes JVM, Aquino JA, Castro TLB, et al. Omeprazole use and risk of chronic kidney disease evolution. PLoS One. 2020;15(3):e0229344. DOI:10.1371/journal.pone.0229344
47. Zhang XY, He QS, Jing Z, et al. Effect of proton pump inhibitors on the risk of chronic kidney disease: A propensity score-based overlap weight analysis using the United Kingdom Biobank. Front Pharmacol. 2022;13:949699. DOI:10.3389/fphar.2022.949699
48. Wu CC, Liao MH, Kung WM, Wang YC. Proton Pump Inhibitors and Risk of Chronic Kidney Disease: Evidence from Observational Studies. J Clin Med. 2023;12(6):2262. DOI:10.3390/jcm12062262
49. Nozaki M, Suzuki T, Hirano M. Rhabdomyolysis associated with omeprazole. J Gastroenterol. 2004;39(1):86. DOI:10.1007/s00535-003-1231-7
50. Bebarta VS, King JA, McDonough M. Proton pump inhibitor-induced rhabdomyolysis and hyponatremic delirium. Am J Emerg Med. 2008;26(4):519.e1-2. DOI:10.1016/j.ajem.2007.08.026
51. Tanaka K, Nakada TA, Abe R, et al. Omeprazole-associated rhabdomyolysis. Crit Care. 2014;18(4):462. DOI:10.1186/s13054-014-0462-8
52. Tröger U, Reiche I, Jepsen MS, et al. Esomeprazole-induced rhabdomyolysis in a patient with heart failure. Intensive Care Med. 2010;36(7):1278-9. DOI:10.1007/s00134-010-1854-0
53. Jeon DH, Kim Y, Kim MJ, et al. Rhabdomyolysis associated with single-dose intravenous esomeprazole administration: A case report. Medicine (Baltimore). 2016;95(29):e4313. DOI:10.1097/MD.0000000000004313
54. Nishikawa J, Hosokawa A, Fuchino M, et al. Rhabdomyolysis associated with long-term treatment of esomeprazole. Nihon Shokakibyo Gakkai Zasshi. 2018;115(3):299-304 [Article in Japanese]. DOI:10.11405/nisshoshi.115.299
55. Ertekin YH, Yakar B, Ertekin H, et al. Diclofenac- and Pantoprazole-Induced Rhabdomyolysis: A Potential Drug Interaction. Drug Saf Case Rep. 2015;2(1):10.
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56. Bourlon S, Veyrac G, Armand C, et al. Rhabdomyolysis during treatment with rabeprazole (Pariel), a proton pump inhibitor combined with domperidone (Peridys). Therapie. 2002;57(6):597-600 [Article in French].
57. Sun Y, Zhang A, Zuo M, et al. A pharmacovigilance study of association between proton-pump inhibitors and rhabdomyolysis event based on FAERS database. J Gastroenterol Hepatol. 2023. DOI:10.1111/jgh.16411
58. Montastruc JL. Rhabdomyolysis and statins: A pharmacovigilance comparative study between statins. Br J Clin Pharmacol. 2023;89(8):2636-8. DOI:10.1111/bcp.15757
59. Mitsuboshi S, Hamano H, Kuniki Y, et al. Proton Pump Inhibitors and Rhabdomyolysis: Analysis of Two Different Cross-Sectional Databases. Ann Pharmacother. 2023;57(11):1255-63. DOI:10.1177/10600280231156270
60. Altebainawi AF, Alfaraj LA, Alharbi AA, et al. Association between proton pump inhibitors and rhabdomyolysis risk: a post-marketing surveillance using FDA adverse event reporting system (FAERS) database. Ther Adv Drug Saf. 2023;14:20420986231154075. DOI:10.1177/20420986231154075
61. Duncan SJ, Howden CW. Proton Pump Inhibitors and Risk of Rhabdomyolysis. Drug Saf. 2017;40(1):61-4. DOI:10.1007/s40264-016-0473-2
62. Haastrup PF, Jarbøl DE, Thompson W, et al. When does proton pump inhibitor treatment become long term? A scoping review. BMJ Open Gastroenterol. 2021;8(1):e000563. DOI:10.1136/bmjgast-2020-000563
63. Freedberg DE, Kim LS, Yang YX. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-15. DOI:10.1053/j.gastro.2017.01.031
64. Targownik LE, Fisher DA, Saini SD. AGA clinical practice update on de-prescribing of proton pump inhibitors: expert review. Gastroenterology. 2022;162(4):1334-42. DOI:10.1053/j.gastro.2021.12.247
65. Vorobyeva NM, Tkacheva ON. Safety of antithrombotic therapy in cardiological practice: how to protect tunica mucosa of gastrointestinal tract? Therapy. 2022;4:134-40 (in Russian). DOI:10.18565/therapy.2022.4.134-140
66. Zhou M, Zhang J, Liu J, et al; CCC-ACS Investigators. Proton Pump Inhibitors and In-Hospital Gastrointestinal Bleeding in Patients With Acute Coronary Syndrome Receiving Dual Antiplatelet Therapy. Mayo Clin Proc. 2022;97(4):682-92. DOI:10.1016/j.mayocp.2021.11.037
67. Tkacheva ON, Vorobyeva NM, Kotovskaya YuV, et al. Antithrombotic therapy in the elderly and senile age: the consensus opinion of experts of the Russian Association of Gerontologists and Geriatricians and the National Society of Preventive Cardiology. Cardiovascular Therapy and Prevention. 2021;20(3):2847 (in Russian).
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68. Experts consensus on reducing the risk of gastrointestinal bleeding in patients receiving oral anticoagulants. Therapy. 2021;7(10):23-41 (in Russian). DOI:10.18565/therapy.2021.10.23–41
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7. Ивашкин В.Т., Маев И.В., Трухманов А.С., и др. Рекомендации Российской гастроэнтерологической ассоциации по диагностике и лечению гастроэзофагеальной рефлюксной болезни. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2020;30(4):70-97 [Ivashkin VT, Maev IV, Trukhmanov AS, et al. Recommendations of the Russian Gastroenterological Association in Diagnosis and Treatment of Gastroesophageal Reflux Disease. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2020;30(4):70-97 (in Russian)]. DOI:10.22416/1382-4376-2020-30-4-70-97
8. Al-Aly Z, Maddukuri G, Xie Y. Proton pump inhibitors and the kidney: implications of current evidence for clinical practice and when and how to deprescribe. Am J Kidney Dis. 2020;75(4):497-507. DOI:10.1053/j.ajkd.2019.07.012
9. Novotny M, Klimova B, Valis M. PPI Long Term Use: Risk of Neurological Adverse Events? Front Neurol. 2019;9:1142. DOI:10.3389/fneur.2018.01142
10. Salvo EM, Ferko NC, Cash SB, et al. Umbrella review of 42 systematic reviews with meta-analyses: the safety of proton pump inhibitors. Aliment Pharmacol Ther. 2021;54(2):129-43. DOI:10.1111/apt.16407
11. Chinzon D, Domingues G, Tosetto N, Perrotti M. Safety of long-term proton pump inhibitors: facts and myths. Arq Gastroenterol. 2022;59(2):219-25.
DOI:10.1590/S0004-2803.202202000-40
12. Maideen NMP. Adverse Effects Associated with Long-Term Use of Proton Pump Inhibitors. Chonnam Med J. 2023;59(2):115-27. DOI:10.4068/cmj.2023.59.2.115
13. Smith CA, Ebrahimpour A, Novikova L, et al. Esomeprazole covalently interacts with the cardiovascular enzyme dimethylarginine dimethylaminohydrolase: Insights into the cardiovascular risk of proton pump inhibitors. Biochim Biophys Acta Gen Subj. 2022;1866(8):130149. DOI:10.1016/j.bbagen.2022.130149
14. Ariel H, Cooke JP. Cardiovascular risk of proton pump inhibitors. Methodist Debakey Cardiovasc J. 2019;15(3):214-9. DOI:10.14797/mdcj-15-3-214
15. Koyyada A. Long-term use of proton pump inhibitors as a risk factor for various adverse manifestations. Therapie. 2021;76(1):13-21. DOI:10.1016/j.therap.2020.06.019
16. Nochaiwong S, Ruengorn C, Awiphan R, et al. The association between proton pump inhibitor use and the risk of adverse kidney outcomes: a systematic review and meta-analysis. Nephrol Dial Transplant. 2018;33(2):331-42. DOI:10.1093/ndt/gfw470
17. Rooney MR, Bell EJ, Alonso A, et al. Proton Pump Inhibitor Use, Hypomagnesemia and Risk of Cardiovascular Diseases: The Atherosclerosis Risk in Communities (ARIC) Study. J Clin Gastroenterol. 2021;55(8):677-83. DOI:10.1097/MCG.0000000000001420
18. Sun S, Cui Z, Zhou M, et al. Proton pump inhibitor monotherapy and the risk of cardiovascular events in patients with gastro-esophageal reflux disease: a meta-analysis. Neurogastroenterol Motil. 2017;29(2):e12926. DOI:10.1111/nmo.12926
19. Bundhun PK, Teeluck AR, Bhurtu A, Huang WQ. Is the concomitant use of clopidogrel and Proton Pump Inhibitors still associated with increased adverse cardiovascular outcomes following coronary angioplasty?: a systematic review and meta-analysis of recently published studies (2012–2016). BMC Cardiovasc Disord. 2017;17(1):3.
DOI:10.1186/s12872-016-0453-6
20. Pang J, Wu Q, Zhang Z, et al. Efficacy and safety of clopidogrel only vs. clopidogrel added proton pump inhibitors in the treatment of patients with coronary heart disease after percutaneous coronary intervention: A systematic review and meta-analysis. Int J Cardiol Heart Vasc. 2019;23:100317. DOI:10.1016/j.ijcha.2018.12.016
21. Freedberg DE, Yang YX, Abrams JA. Proton pump inhibitors and myocardial infarction. Gastroenterology. 2015;149(4):830-3. DOI:10.1053/j.gastro.2015.08.002
22. Tseng HJ, Cheng CM, Tsai SJ, et al. Proton pump inhibitor exposure and acute myocardial infarction risk: a nested cohort study. Cardiovasc Toxicol. 2021;21(6):444-50. DOI:10.1007/s12012-021-09637-2
23. Qian Y, Jick S. Proton-pump inhibitor use and myocardial infarction: a nested case-control study in the UK Clinical Practice Research Datalink. Epidemiology.
2020;31(3):423-31. DOI:10.1097/EDE.0000000000001152
24. Ghebremariam YT, LePendu P, Lee JC, et al. Unexpected effect of proton pump inhibitors: elevation of the cardiovascular risk factor asymmetric dimethylarginine. Circulation. 2013;128(8):845-53. DOI:10.1161/CIRCULATIONAHA.113.003602
25. Kang MK, Shin JH, Kim TJ, et al. Use of proton pump inhibitor may be associated with progression of cerebral small vessel disease. PLoS One. 2022;17(12):e0279257. DOI:10.1371/journal.pone.0279257
26. Sehested TSG, Gerds TA, Fosbøl EL, et al. Long-term use of proton pump inhibitors, dose-response relationship and associated risk of ischemic stroke and myocardial infarction. J Intern Med. 2018;283(3):268-81. DOI:10.1111/joim.12698
27. Wang YF, Chen YT, Luo JC, et al. Proton-pump inhibitor use and the risk of first-time ischemic stroke in the general population: a nationwide population-based study. Am J Gastroenterol. 2017;112(7):1084-93. DOI:10.1038/ajg.2017.101
28. Yang M, He Q, Gao F, et al. Regular use of proton-pump inhibitors and risk of stroke: a population-based cohort study and meta-analysis of randomized-controlled trials. BMC Med. 2021;19(1):316. DOI:10.1186/s12916-021-02180-5
29. Li S, Liu F, Chen C, et al. Real-world relationship between proton pump inhibitors and cerebro-cardiovascular outcomes independent of clopidogrel. Int Heart J.
2019;60(4):910-8. DOI:10.1536/ihj.18-584
30. Farhat N, Fortin Y, Haddad N, et al. Systematic review and meta-analysis of adverse cardiovascular events associated with proton pump inhibitors used alone or in combination with antiplatelet agents. Crit Rev Toxicol. 2019;49(3):215-61. DOI:10.1080/10408444.2019.1583167
31. Nolde M, Ahn N, Dreischulte T, et al. The long-term risk for myocardial infarction or stroke after proton pump inhibitor therapy (2008–2018). Aliment Pharmacol Ther. 2021;54(8):1033-40. DOI:10.1111/apt.16565
32. Shang YS, Zhong PY, Ma Y, et al. Efficacy and safety of proton pump inhibitors in patients with coronary artery diseases receiving oral antiplatelet agents and/or anticoagulants: A systematic review and meta-analysis. J Cardiovasc Pharmacol. 2022;80(1):1-12. DOI:10.1097/FJC.0000000000001284
33. Nolde M, Ahn N, Dreischulte T, et al. Proton pump inhibitors and the risk of cardiovascular events and cardiovascular mortality: a systematic review and meta-analysis of observational studies. Eur J Intern Med. 2022;106:80-9. DOI:10.1016/j.ejim.2022.09.021
34. Chui CSL, Cheung KS, Brown JP, et al. Proton pump inhibitors and myocardial infarction: an application of active comparators in a self-controlled case series. Int J Epidemiol. 2023;52(3):899-907. DOI:10.1093/ije/dyac196
35. Yuan J, He Q, Nguyen LH, et al. Regular use of proton pump inhibitors and risk of type 2 diabetes: results from three prospective cohort studies. Gut.
2021;70(6):1070-7. DOI:10.1136/gutjnl-2020-322557
36. Czarniak P, Ahmadizar F, Hughes J, et al. Proton pump inhibitors are associated with incident type 2 diabetes mellitus in a prospective population-based cohort study. Br J Clin Pharmacol. 2022;88(6):2718-26. DOI:10.1111/bcp.15182
37. Ciardullo S, Rea F, Savaré L, et al. Prolonged Use of Proton Pump Inhibitors and Risk of Type 2 Diabetes: Results From a Large Population-Based Nested Case-Control Study. J Clin Endocrinol Metab. 2022;107(7):e2671-9. DOI:10.1210/clinem/dgac231
38. Guo YR, Liu XM, Wang GX. Exposure to proton pump inhibitors and risk of diabetes: A systematic review and meta-analysis. World J Diabetes. 2023;14(2):120-9. DOI:10.4239/wjd.v14.i2.120
39. Schiffl H, Al-Nemnem E, Lang SM. Proton-pump inhibitors and chronic kidney disease: hidden consequences of an inappropriate drug use? Saudi J Kidney Dis Transpl. 2020;31(2):312-9. DOI:10.4103/1319-2442.284005
40. Arora P, Gupta A, Golzy M, et al. Proton pump inhibitors are associated with increased risk of development of chronic kidney disease. BMC Nephrol. 2016;17(1):112. DOI:10.1186/s12882-016-0325-4
41. 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. DOI:10.1001/jamainternmed.2015.7193
42. Xie Y, Bowe B, Li T, et al. Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury. Kidney Int.
2017;91(6):1482-94. DOI:10.1016/j.kint.2016.12.021
43. Yang H, Juang SY, Liao KF. Proton pump inhibitors use and risk of chronic kidney disease in diabetic patients. Diabetes Res Clin Pract. 2019;147:67-75. DOI:10.1016/j.diabres.2018.11.019
44. Hart E, Dunn TE, Feuerstein S, Jacobs DM. Proton Pump Inhibitors and Risk of Acute and Chronic Kidney Disease: A Retrospective Cohort Study. Pharmacotherapy.
2019;39(4):443-53. DOI:10.1002/phar.2235
45. Rodríguez-Poncelas A, Barceló MA, Saez M, Coll-de-Tuero G. Duration and dosing of proton pump inhibitors associated with high incidence of chronic kidney disease in population-based cohort. PLoS One. 2018;13(10):e0204231. DOI:10.1371/journal.pone.0204231
46. Guedes JVM, Aquino JA, Castro TLB, et al. Omeprazole use and risk of chronic kidney disease evolution. PLoS One. 2020;15(3):e0229344. DOI:10.1371/journal.pone.0229344
47. Zhang XY, He QS, Jing Z, et al. Effect of proton pump inhibitors on the risk of chronic kidney disease: A propensity score-based overlap weight analysis using the United Kingdom Biobank. Front Pharmacol. 2022;13:949699. DOI:10.3389/fphar.2022.949699
48. Wu CC, Liao MH, Kung WM, Wang YC. Proton Pump Inhibitors and Risk of Chronic Kidney Disease: Evidence from Observational Studies. J Clin Med. 2023;12(6):2262. DOI:10.3390/jcm12062262
49. Nozaki M, Suzuki T, Hirano M. Rhabdomyolysis associated with omeprazole. J Gastroenterol. 2004;39(1):86. DOI:10.1007/s00535-003-1231-7
50. Bebarta VS, King JA, McDonough M. Proton pump inhibitor-induced rhabdomyolysis and hyponatremic delirium. Am J Emerg Med. 2008;26(4):519.e1-2. DOI:10.1016/j.ajem.2007.08.026
51. Tanaka K, Nakada TA, Abe R, et al. Omeprazole-associated rhabdomyolysis. Crit Care. 2014;18(4):462. DOI:10.1186/s13054-014-0462-8
52. Tröger U, Reiche I, Jepsen MS, et al. Esomeprazole-induced rhabdomyolysis in a patient with heart failure. Intensive Care Med. 2010;36(7):1278-9. DOI:10.1007/s00134-010-1854-0
53. Jeon DH, Kim Y, Kim MJ, et al. Rhabdomyolysis associated with single-dose intravenous esomeprazole administration: A case report. Medicine (Baltimore). 2016;95(29):e4313. DOI:10.1097/MD.0000000000004313
54. Nishikawa J, Hosokawa A, Fuchino M, et al. Rhabdomyolysis associated with long-term treatment of esomeprazole. Nihon Shokakibyo Gakkai Zasshi. 2018;115(3):299-304 [Article in Japanese]. DOI:10.11405/nisshoshi.115.299
55. Ertekin YH, Yakar B, Ertekin H, et al. Diclofenac- and Pantoprazole-Induced Rhabdomyolysis: A Potential Drug Interaction. Drug Saf Case Rep. 2015;2(1):10.
DOI:10.1007/s40800-015-0012-6
56. Bourlon S, Veyrac G, Armand C, et al. Rhabdomyolysis during treatment with rabeprazole (Pariel), a proton pump inhibitor combined with domperidone (Peridys). Therapie. 2002;57(6):597-600 [Article in French].
57. Sun Y, Zhang A, Zuo M, et al. A pharmacovigilance study of association between proton-pump inhibitors and rhabdomyolysis event based on FAERS database. J Gastroenterol Hepatol. 2023. DOI:10.1111/jgh.16411
58. Montastruc JL. Rhabdomyolysis and statins: A pharmacovigilance comparative study between statins. Br J Clin Pharmacol. 2023;89(8):2636-8. DOI:10.1111/bcp.15757
59. Mitsuboshi S, Hamano H, Kuniki Y, et al. Proton Pump Inhibitors and Rhabdomyolysis: Analysis of Two Different Cross-Sectional Databases. Ann Pharmacother. 2023;57(11):1255-63. DOI:10.1177/10600280231156270
60. Altebainawi AF, Alfaraj LA, Alharbi AA, et al. Association between proton pump inhibitors and rhabdomyolysis risk: a post-marketing surveillance using FDA adverse event reporting system (FAERS) database. Ther Adv Drug Saf. 2023;14:20420986231154075. DOI:10.1177/20420986231154075
61. Duncan SJ, Howden CW. Proton Pump Inhibitors and Risk of Rhabdomyolysis. Drug Saf. 2017;40(1):61-4. DOI:10.1007/s40264-016-0473-2
62. Haastrup PF, Jarbøl DE, Thompson W, et al. When does proton pump inhibitor treatment become long term? A scoping review. BMJ Open Gastroenterol. 2021;8(1):e000563. DOI:10.1136/bmjgast-2020-000563
63. Freedberg DE, Kim LS, Yang YX. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-15. DOI:10.1053/j.gastro.2017.01.031
64. Targownik LE, Fisher DA, Saini SD. AGA clinical practice update on de-prescribing of proton pump inhibitors: expert review. Gastroenterology. 2022;162(4):1334-42. DOI:10.1053/j.gastro.2021.12.247
65. Воробьева Н.М., Ткачева О.Н. Безопасность антитромботической терапии в кардиологической практике: как защитить слизистую желудочно-кишечного тракта? Терапия. 2022;4:134-40 [Vorobyeva NM, Tkacheva ON. Safety of antithrombotic therapy in cardiological practice: how to protect tunica mucosa of gastrointestinal tract? Therapy. 2022;4:134-40 (in Russian)]. DOI:10.18565/therapy.2022.4.134-140
66. Zhou M, Zhang J, Liu J, et al; CCC-ACS Investigators. Proton Pump Inhibitors and In-Hospital Gastrointestinal Bleeding in Patients With Acute Coronary Syndrome Receiving Dual Antiplatelet Therapy. Mayo Clin Proc. 2022;97(4):682-92. DOI:10.1016/j.mayocp.2021.11.037
67. Ткачева О.Н., Воробьева Н.М., Котовская Ю.В., и др. Антитромботическая терапия в пожилом и старческом возрасте: согласованное мнение экспертов Российской ассоциации геронтологов и гериатров и Национального общества профилактической кардиологии. Кардиоваскулярная терапия и профилактика. 2021;20(3):2847 [Tkacheva ON, Vorobyeva NM, Kotovskaya YuV, et al. Antithrombotic therapy in the elderly and senile age: the consensus opinion of experts of the Russian Association of Gerontologists and Geriatricians and the National Society of Preventive Cardiology. Cardiovascular Therapy and Prevention. 2021;20(3):2847 (in Russian)]. DOI:10.15829/1728-8800-2021-2847
68. Консенсус экспертов по снижению риска желудочно-кишечных кровотечений у пациентов, получающих оральные антикоагулянты. Терапия. 2021;7(10):23-41 [Experts consensus on reducing the risk of gastrointestinal bleeding in patients receiving oral anticoagulants. Therapy. 2021;7(10):23-41 (in Russian)]. DOI:10.18565/therapy.2021.10.23–41
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17. Rooney MR, Bell EJ, Alonso A, et al. Proton Pump Inhibitor Use, Hypomagnesemia and Risk of Cardiovascular Diseases: The Atherosclerosis Risk in Communities (ARIC) Study. J Clin Gastroenterol. 2021;55(8):677-83. DOI:10.1097/MCG.0000000000001420
18. Sun S, Cui Z, Zhou M, et al. Proton pump inhibitor monotherapy and the risk of cardiovascular events in patients with gastro-esophageal reflux disease: a meta-analysis. Neurogastroenterol Motil. 2017;29(2):e12926. DOI:10.1111/nmo.12926
19. Bundhun PK, Teeluck AR, Bhurtu A, Huang WQ. Is the concomitant use of clopidogrel and Proton Pump Inhibitors still associated with increased adverse cardiovascular outcomes following coronary angioplasty?: a systematic review and meta-analysis of recently published studies (2012–2016). BMC Cardiovasc Disord. 2017;17(1):3.
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20. Pang J, Wu Q, Zhang Z, et al. Efficacy and safety of clopidogrel only vs. clopidogrel added proton pump inhibitors in the treatment of patients with coronary heart disease after percutaneous coronary intervention: A systematic review and meta-analysis. Int J Cardiol Heart Vasc. 2019;23:100317. DOI:10.1016/j.ijcha.2018.12.016
21. Freedberg DE, Yang YX, Abrams JA. Proton pump inhibitors and myocardial infarction. Gastroenterology. 2015;149(4):830-3. DOI:10.1053/j.gastro.2015.08.002
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26. Sehested TSG, Gerds TA, Fosbøl EL, et al. Long-term use of proton pump inhibitors, dose-response relationship and associated risk of ischemic stroke and myocardial infarction. J Intern Med. 2018;283(3):268-81. DOI:10.1111/joim.12698
27. Wang YF, Chen YT, Luo JC, et al. Proton-pump inhibitor use and the risk of first-time ischemic stroke in the general population: a nationwide population-based study. Am J Gastroenterol. 2017;112(7):1084-93. DOI:10.1038/ajg.2017.101
28. Yang M, He Q, Gao F, et al. Regular use of proton-pump inhibitors and risk of stroke: a population-based cohort study and meta-analysis of randomized-controlled trials. BMC Med. 2021;19(1):316. DOI:10.1186/s12916-021-02180-5
29. Li S, Liu F, Chen C, et al. Real-world relationship between proton pump inhibitors and cerebro-cardiovascular outcomes independent of clopidogrel. Int Heart J.
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31. Nolde M, Ahn N, Dreischulte T, et al. The long-term risk for myocardial infarction or stroke after proton pump inhibitor therapy (2008–2018). Aliment Pharmacol Ther. 2021;54(8):1033-40. DOI:10.1111/apt.16565
32. Shang YS, Zhong PY, Ma Y, et al. Efficacy and safety of proton pump inhibitors in patients with coronary artery diseases receiving oral antiplatelet agents and/or anticoagulants: A systematic review and meta-analysis. J Cardiovasc Pharmacol. 2022;80(1):1-12. DOI:10.1097/FJC.0000000000001284
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34. Chui CSL, Cheung KS, Brown JP, et al. Proton pump inhibitors and myocardial infarction: an application of active comparators in a self-controlled case series. Int J Epidemiol. 2023;52(3):899-907. DOI:10.1093/ije/dyac196
35. Yuan J, He Q, Nguyen LH, et al. Regular use of proton pump inhibitors and risk of type 2 diabetes: results from three prospective cohort studies. Gut.
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37. Ciardullo S, Rea F, Savaré L, et al. Prolonged Use of Proton Pump Inhibitors and Risk of Type 2 Diabetes: Results From a Large Population-Based Nested Case-Control Study. J Clin Endocrinol Metab. 2022;107(7):e2671-9. DOI:10.1210/clinem/dgac231
38. Guo YR, Liu XM, Wang GX. Exposure to proton pump inhibitors and risk of diabetes: A systematic review and meta-analysis. World J Diabetes. 2023;14(2):120-9. DOI:10.4239/wjd.v14.i2.120
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41. 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. DOI:10.1001/jamainternmed.2015.7193
42. Xie Y, Bowe B, Li T, et al. Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury. Kidney Int.
2017;91(6):1482-94. DOI:10.1016/j.kint.2016.12.021
43. Yang H, Juang SY, Liao KF. Proton pump inhibitors use and risk of chronic kidney disease in diabetic patients. Diabetes Res Clin Pract. 2019;147:67-75. DOI:10.1016/j.diabres.2018.11.019
44. Hart E, Dunn TE, Feuerstein S, Jacobs DM. Proton Pump Inhibitors and Risk of Acute and Chronic Kidney Disease: A Retrospective Cohort Study. Pharmacotherapy.
2019;39(4):443-53. DOI:10.1002/phar.2235
45. Rodríguez-Poncelas A, Barceló MA, Saez M, Coll-de-Tuero G. Duration and dosing of proton pump inhibitors associated with high incidence of chronic kidney disease in population-based cohort. PLoS One. 2018;13(10):e0204231. DOI:10.1371/journal.pone.0204231
46. Guedes JVM, Aquino JA, Castro TLB, et al. Omeprazole use and risk of chronic kidney disease evolution. PLoS One. 2020;15(3):e0229344. DOI:10.1371/journal.pone.0229344
47. Zhang XY, He QS, Jing Z, et al. Effect of proton pump inhibitors on the risk of chronic kidney disease: A propensity score-based overlap weight analysis using the United Kingdom Biobank. Front Pharmacol. 2022;13:949699. DOI:10.3389/fphar.2022.949699
48. Wu CC, Liao MH, Kung WM, Wang YC. Proton Pump Inhibitors and Risk of Chronic Kidney Disease: Evidence from Observational Studies. J Clin Med. 2023;12(6):2262. DOI:10.3390/jcm12062262
49. Nozaki M, Suzuki T, Hirano M. Rhabdomyolysis associated with omeprazole. J Gastroenterol. 2004;39(1):86. DOI:10.1007/s00535-003-1231-7
50. Bebarta VS, King JA, McDonough M. Proton pump inhibitor-induced rhabdomyolysis and hyponatremic delirium. Am J Emerg Med. 2008;26(4):519.e1-2. DOI:10.1016/j.ajem.2007.08.026
51. Tanaka K, Nakada TA, Abe R, et al. Omeprazole-associated rhabdomyolysis. Crit Care. 2014;18(4):462. DOI:10.1186/s13054-014-0462-8
52. Tröger U, Reiche I, Jepsen MS, et al. Esomeprazole-induced rhabdomyolysis in a patient with heart failure. Intensive Care Med. 2010;36(7):1278-9. DOI:10.1007/s00134-010-1854-0
53. Jeon DH, Kim Y, Kim MJ, et al. Rhabdomyolysis associated with single-dose intravenous esomeprazole administration: A case report. Medicine (Baltimore). 2016;95(29):e4313. DOI:10.1097/MD.0000000000004313
54. Nishikawa J, Hosokawa A, Fuchino M, et al. Rhabdomyolysis associated with long-term treatment of esomeprazole. Nihon Shokakibyo Gakkai Zasshi. 2018;115(3):299-304 [Article in Japanese]. DOI:10.11405/nisshoshi.115.299
55. Ertekin YH, Yakar B, Ertekin H, et al. Diclofenac- and Pantoprazole-Induced Rhabdomyolysis: A Potential Drug Interaction. Drug Saf Case Rep. 2015;2(1):10.
DOI:10.1007/s40800-015-0012-6
56. Bourlon S, Veyrac G, Armand C, et al. Rhabdomyolysis during treatment with rabeprazole (Pariel), a proton pump inhibitor combined with domperidone (Peridys). Therapie. 2002;57(6):597-600 [Article in French].
57. Sun Y, Zhang A, Zuo M, et al. A pharmacovigilance study of association between proton-pump inhibitors and rhabdomyolysis event based on FAERS database. J Gastroenterol Hepatol. 2023. DOI:10.1111/jgh.16411
58. Montastruc JL. Rhabdomyolysis and statins: A pharmacovigilance comparative study between statins. Br J Clin Pharmacol. 2023;89(8):2636-8. DOI:10.1111/bcp.15757
59. Mitsuboshi S, Hamano H, Kuniki Y, et al. Proton Pump Inhibitors and Rhabdomyolysis: Analysis of Two Different Cross-Sectional Databases. Ann Pharmacother. 2023;57(11):1255-63. DOI:10.1177/10600280231156270
60. Altebainawi AF, Alfaraj LA, Alharbi AA, et al. Association between proton pump inhibitors and rhabdomyolysis risk: a post-marketing surveillance using FDA adverse event reporting system (FAERS) database. Ther Adv Drug Saf. 2023;14:20420986231154075. DOI:10.1177/20420986231154075
61. Duncan SJ, Howden CW. Proton Pump Inhibitors and Risk of Rhabdomyolysis. Drug Saf. 2017;40(1):61-4. DOI:10.1007/s40264-016-0473-2
62. Haastrup PF, Jarbøl DE, Thompson W, et al. When does proton pump inhibitor treatment become long term? A scoping review. BMJ Open Gastroenterol. 2021;8(1):e000563. DOI:10.1136/bmjgast-2020-000563
63. Freedberg DE, Kim LS, Yang YX. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-15. DOI:10.1053/j.gastro.2017.01.031
64. Targownik LE, Fisher DA, Saini SD. AGA clinical practice update on de-prescribing of proton pump inhibitors: expert review. Gastroenterology. 2022;162(4):1334-42. DOI:10.1053/j.gastro.2021.12.247
65. Vorobyeva NM, Tkacheva ON. Safety of antithrombotic therapy in cardiological practice: how to protect tunica mucosa of gastrointestinal tract? Therapy. 2022;4:134-40 (in Russian). DOI:10.18565/therapy.2022.4.134-140
66. Zhou M, Zhang J, Liu J, et al; CCC-ACS Investigators. Proton Pump Inhibitors and In-Hospital Gastrointestinal Bleeding in Patients With Acute Coronary Syndrome Receiving Dual Antiplatelet Therapy. Mayo Clin Proc. 2022;97(4):682-92. DOI:10.1016/j.mayocp.2021.11.037
67. Tkacheva ON, Vorobyeva NM, Kotovskaya YuV, et al. Antithrombotic therapy in the elderly and senile age: the consensus opinion of experts of the Russian Association of Gerontologists and Geriatricians and the National Society of Preventive Cardiology. Cardiovascular Therapy and Prevention. 2021;20(3):2847 (in Russian).
DOI:10.15829/1728-8800-2021-2847
68. Experts consensus on reducing the risk of gastrointestinal bleeding in patients receiving oral anticoagulants. Therapy. 2021;7(10):23-41 (in Russian). DOI:10.18565/therapy.2021.10.23–41
Авторы
Д.И. Трухан*1, С.Н. Филимонов2,3
1ФГБОУ ВО «Омский государственный медицинский университет» Минздрава России, Омск, Россия;
2ФГБНУ «Научно-исследовательский институт комплексных проблем гигиены и профессиональных заболеваний» Минобрнауки России, Новокузнецк, Россия;
3Новокузнецкий государственный институт усовершенствования врачей – филиал ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Новокузнецк, Россия
*dmitry_trukhan@mail.ru
1Omsk State Medical University, Omsk, Russia;
2Research Institute for Complex Problems of Hygiene and Occupational Diseases, Novokuznetsk, Russia;
3Novokuznetsk State Institute for Further Training of Physicians – Branch Campus of the Russian Medical Academy of Continuous Professional Education, Novokuznetsk, Russia
*dmitry_trukhan@mail.ru
1ФГБОУ ВО «Омский государственный медицинский университет» Минздрава России, Омск, Россия;
2ФГБНУ «Научно-исследовательский институт комплексных проблем гигиены и профессиональных заболеваний» Минобрнауки России, Новокузнецк, Россия;
3Новокузнецкий государственный институт усовершенствования врачей – филиал ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Новокузнецк, Россия
*dmitry_trukhan@mail.ru
________________________________________________
1Omsk State Medical University, Omsk, Russia;
2Research Institute for Complex Problems of Hygiene and Occupational Diseases, Novokuznetsk, Russia;
3Novokuznetsk State Institute for Further Training of Physicians – Branch Campus of the Russian Medical Academy of Continuous Professional Education, Novokuznetsk, Russia
*dmitry_trukhan@mail.ru
Цель портала OmniDoctor – предоставление профессиональной информации врачам, провизорам и фармацевтам.