Прием ингибиторов протонной помпы и прогноз пациентов после плановых чрескожных коронарных вмешательств

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Аннотация

Цель исследования – изучить взаимосвязь между приемом ингибиторов протонной помпы (ИПП) и риском развития тромботических осложнений у больных, подвергаемых плановым процедурам чрескожных коронарных вмешательств (ЧКВ) и получающих двойную антиагрегантную терапию.
Материалы и методы. Исследование представляет собой проспективный регистр пациентов, которым успешно выполнено плановое ЧКВ. Влияние приема ИПП (омепразола и пантопразола) на частоту комбинированной конечной точки: сердечно-сосудистая смерть, острый коронарный синдром, ишемический инсульт, транзиторная ишемическая атака, тромбоз периферических артерий и тромбоэмболия легочной артерии – оценивали с помощью критерия Log-Rank, а также в рамках многофакторного анализа (регрессионная модель пропорционального риска Кокса).
Результаты. Всего в исследование включен 391 пациент (23,1% женщины, средний возраст 61,2 ± 10,4 года). Медиана длительности наблюдения составила 18 мес. За этот период времени зарегистрировано 34 неблагоприятных события. Log-Rank-анализ показал, что доля пациентов без неблагоприятных событий в группе омепразола достоверно ниже в сравнении с пациентами, не получающими ИПП (0,56 против 0,84, Log-Rank p=0,003), а для пантопразола такой закономерности не выявлено (0,89 против 0,84, Log-Rank p=0,21). Средний уровень остаточной реактивности тромбоцитов (ОРТ), а также число больных с высокой ОРТ (>208 PRU) достоверно не различались между группами омепразола, пантопразола и группой пациентов, не получающих ИПП. По данным многофакторного анализа, прием омепразола оказался независимым предиктором развития тромботических осложнений после планового ЧКВ (отношение шансов 3,75, 95% доверительный интервал 1,72–8,17, р=0,0009).
Заключение. Длительный прием омепразола (не менее 30 сут) является независимым предиктором тромботических осложнений у пациентов, перенесших плановое ЧКВ.

Ключевые слова: ингибиторы протонной помпы, омепразол, пантопразол, ишемическая болезнь сердца, чрескожные коронарные вмешательства, риск сердечно-сосудистых осложнений.

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The urgency of the study is determined by the lack of data necessary in order to assess the safety of prolonged use of proton pump inhibitors (PPI) in patients with IHD combined with anti-aggregant therapy.
The aim of the study was to study the relationship between the use of PPI and the risk of thrombotic complications in patients undergoing planned procedures of percutaneous coronary interventions (PCI) and receiving dual antiplatelet therapy.
Materials and methods. The study is a prospective register of patients who successfully underwent planned percutaneous coronary intervention (PCI). The effect of PPI (omeprazole and pantoprazole) on the frequency of the combined end point cardiovascular death, ACS, AI, TIA, peripheral arterial thrombosis and PE was assessed using the Log-Rank criterion, as well as in a multivariate analysis (Cox proportional risk regression model).
Results. A total of 391 patients were included in the study (23.1% women, mean age 61.2 [Symbol] 10.4 years). The median duration of follow-up was 18 months. During this period of time, 34 adverse events were recorded. Log-Rank analysis showed that the proportion of patients without adverse events in the omeprazole group was significantly lower in comparison with patients who did not receive PPI (0.56 vs. 0.84, Log-Rank p=0.003), and for pantoprazole no such pattern was found (0.89 against 0.84, Log-Rank p=0.21). The average level of residual platelet reactivity (ORT), as well as the number of patients with high ORT (> 208 PRU), did not differ significantly between the groups of omeprazole, pantoprazole and the group of patients not receiving PPI. According to multivariate analysis, omeprazole was an independent predictor of thrombotic complications after a planned PCI (OR 3.75, 95% confidence interval 1.72-8.17, p=-0.0009).
Conclusion. Long-term use of omeprazole (at least 30 days) is an independent predictor of thrombotic complications in patients who underwent planned PCI.

Keywords: proton pump inhibitors, omeprazole, pantoprazole, IHD, percutaneous coronary interventions, risk of cardiovascular complications.

Список литературы

1. Valgimigli M, Bueno H, Byrne R, et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. Europ J Cardio-Thoracic Surgery. 2017;53(1):34-78. doi:10.1093/ejcts/ezx334
2. Steffel J, Verhamme P, Potpara T, 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):1330-193. doi:10.1093/eurheartj/ehy136
3. Harjai K, Shenoy C, Orshaw P, Usmani S, Boura J, Mehta R. Clinical Outcomes in Patients With the Concomitant Use of Clopidogrel and Proton Pump Inhibitors After Percutaneous Coronary Intervention: An Analysis From the Guthrie Health Off-Label Stent (GHOST) Investigators. Circulation: Cardiovascular Interventions. 2011;4(2):162-70. doi:10.1161/circinterventions.110.958884
4. Juurlink D, Gomes T, Ko D, et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. Can Med Assoc J. 2009;180(7):713-18. doi:10.1503/cmaj.082001
5. Schmidt M, Johansen M, Robertson D, et al. Concomitant use of clopidogrel and proton pump inhibitors is not associated with major adverse cardiovascular events following coronary stent implantation. Aliment Pharmacol Ther. 2011;35(1):165-74. doi:10.1111/j.1365-2036.2011. 04890.x
6. Simon T, Steg P, Gilard M, et al. Clinical Events as a Function of Proton Pump Inhibitor Use, Clopidogrel Use, and Cytochrome P450 2C19 Genotype in a Large Nationwide Cohort of Acute Myocardial Infarction: Results From the French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) Registry. Circulation. 2011;123(5):474-82. doi:10.1161/circulationaha.110.965640
7. van Boxel O, van Oijen M, Hagenaars M, Smout A, Siersema P. Cardiovascular and Gastrointestinal Outcomes in Clopidogrel Users on Proton Pump Inhibitors: Results of a Large Dutch Cohort Study. Am J Gastroenterol. 2010;105(11):2430-36. doi:10.1038/ajg.2010.334
8. Charlot M, Ahlehoff O, Jorgensen C, et al. Proton pump inhibitors are associated with cardiovascular risk independent of clopidogrel use in patients with myocardial infarction: a nationwide propensity score matched study. J Am Coll Cardiol. 2010;55(10):A108.E1005. doi:10.1016/s0735-1097(10)61006-6
9. Schmidt M, Johansen M, Robertson D, et al. Concomitant use of clopidogrel and proton pump inhibitors is not associated with major adverse cardiovascular events following coronary stent implantation. Aliment Pharmacol Ther. 2011;35(1):165-74. doi:10.1111/j.1365-2036.2011. 04890.x
10. Valkhoff V,‘t Jong G, Van Soest E, Kuipers E, Sturkenboom M. Risk of recurrent myocardial infarction with the concomitant use of clopidogrel and proton pump inhibitors. Aliment Pharmacol Ther. 2010;33(1):77-88. doi:10.1111/j.1365-2036.2010.04485.x
11. Cardoso R, Benjo A, DiNicolantonio J, et al. Incidence of cardiovascular events and gastrointestinal bleeding in patients receiving clopidogrel with and without proton pump inhibitors: an updated meta-analysis. Open Heart. 2015;2(1):e000248. doi:10.1136/openhrt-2015-000248
12. Wedemeyer R, Blume H. Pharmacokinetic Drug Interaction Profiles of Proton Pump Inhibitors: An Update. Drug Saf. 2014;37(4):201-11. doi:10.1007/s40264-014-0144-0
13. Angiolillo D, Gibson C, Cheng S, et al. Differential Effects of Omeprazole and Pantoprazole on the Pharmacodynamics and Pharmacokinetics of Clopidogrel in Healthy Subjects: Randomized, Placebo-Controlled, Crossover Comparison Studies. Clinical Pharmacology & Therapeutics. 2010;89(1):65-74. doi:10.1038/clpt.2010.219
14. Hokimoto S, Mizobe M, Akasaka T, et al. Impact of CYP2C19 Polymorphism and Proton Pump Inhibitors on Platelet Reactivity to Clopidogrel and Clinical Outcomes Following Stent Implantation. Thromb Res. 2014;133(4):599-605. doi:10.1016/j.thromres.2014.01.003
15. Frelinger A, Lee R, Mulford D, et al. A Randomized, 2-Period, Crossover Design Study to Assess the Effects of Dexlansoprazole, Lansoprazole, Esomeprazole, and Omeprazole on the Steady-State Pharmacokinetics and Pharmacodynamics of Clopidogrel in Healthy Volunteers. J Am Coll Cardiol. 2012;59(14):1304-11. doi:10.1016/j. jacc.2011.12.024
16. Information for Healthcare Professionals: Update to the labeling of Clopidogrel Bisulfate (marketed as Plavix) to alert healthcare professionals about a drug interaction with omeprazole (marketed as Prilosec and Prilosec OTC) [Ссылка доступна на 23.05.2018];2009 http://www.pdr.net/fda-drug-safety-communication/plavix?druglabelid= 525&id=5033
17. Sherwood MW, Melloni C, Jones WS, et al. Individual proton pump inhibitors and outcomes in patients with coronary artery disease on dual antiplatelet therapy: a systematic review. J Am Heart Assoc. 2015;4(11):e002245. doi: 10.1161/JAHA.115.002245
18. Pello Lázaro A, Cristóbal C, Franco-Peláez J, et al. Use of Proton-Pump Inhibitors Predicts Heart Failure and Death in Patients with Coronary Artery Disease. PLoS ONE. 2017;12(1):e0169826. doi:10. 1371/journal.pone.0169826
19. Bhatt DL, Cryer BL, Contant CF, et al. Clopidogrel with or without Omeprazole in Coronary Disease. New England J Medicine. 2011; 364(7):681-83. doi:10.1056/nejmc1013859
20. Hsu P, Lai K, Liu C. Esomeprazole With Clopidogrel Reduces Peptic Ulcer Recurrence, Compared With Clopidogrel Alone, in Patients With Atherosclerosis. Gastroenterology. 2011;140(3):791-8.e2. doi:10.1053/j.gastro.2010.11.056
21. Hsu P. Proton Pump Inhibitor Prevents Clinically Significant Upper Gastrointestinal Evetns in Clopidogrel Users With Ulcer History. Gastroenterology. 2012;142(5):S-27. doi:10.1016/s0016-5085(12)60109-7
22. Vaduganathan M, Cannon C, Cryer B, et al. Efficacy and Safety of Proton-Pump Inhibitors in High-Risk Cardiovascular Subsets of the COGENT Trial. Am J Med. 2016;129(9):1002-5. doi:10.1016/j.amjmed. 2016.03.042
23. Bhurke S, Martin B, Li C, Franks A, Bursac Z, Said Q. Effect of the Clopidogrel-Proton Pump Inhibitor Drug Interaction on Adverse Cardiovascular Events in Patients with Acute Coronary Syndrome. Pharmacotherapy: J Human Pharmacology and Drug Therapy. 2012; 32(9):809-18. doi:10.1002/j.1875-9114.2012.01112.x
24. Chandrasekhar J, Bansilal S, Baber U, et al. Impact of proton pump inhibitors and dual antiplatelet therapy cessation on outcomes following percutaneous coronary intervention: Results From the PARIS Registry. Catheterization and Cardiovascular Interventions. 2016;89(7):E217-E225. doi:10.1002/ccd.26716
25. Комаров А.Л. Факторы, определяющие прогноз и эффективность антитромбоцитарной терапии у больных хронической ишемической болезнью сердца. Дисс. ... М., 2013. Доступно по: http://cardioweb.ru/files/autoref/%D0%B0%D0%B2%D1%82%D0%BE%D1
%80%D0%B5%D1%84%D0%B5%D1%80%D0%B0%D1%82%20
%D0%B4%D0%BC%D0%BD%20%D0%9A%D0%BE%D0%BC%
D0%B0%D1%80%D0%BE%D0%B2%20%D0%90.%D0%9B..pdf. Ссылка активна на 23.05.2018 [Komarov A.L. Factors determining the prognosis and effectiveness of antiplatelet therapy in patients with chronic ischemic heart disease. Thesis for a doctor of medicsl sciences degree M., 2013 (In Russ.)]. Available at: http://cardioweb.ru/files/autoref/%D0%B0%D0%B2%D1%82%D0%BE%D1%80%D0%B5%D
1%84%D0%B5% D1% 80% D0% B0% D1% 82% 20% D0% B4% D0% BC% D0% BD% 20% D0% 9A% D0% BE% D0% BC% D0% B0% D1% 80% D0% BE% D0% B2% 20% D0% 90.% D0% 9B..pdf. The link is active on May 23, 2018
26. Sukhovershin RA, Cooke JP. How may proton pump inhibitors impair cardiovascular health? Amer J Cardiovascular drugs : drugs, devices, and other interventions. 2016;16(3):153-61. doi:10.1007/s40256-016-0160-9
27. Goodman S, Clare R, Pieper K, et al. Association of Proton Pump Inhibitor Use on Cardiovascular Outcomes With Clopidogrel and Ticagrelor: Insights From the Platelet Inhibition and Patient Outcomes Trial. Circulation. 2012;125(8):978-86. doi:10.1161/circulationaha.111. 032912
28. Shah N, LePendu P, Bauer-Mehren A, et al. Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population. PLoS ONE. 2015;10(6):e0124653. doi:10.1371/journal.pone.0124653
29. Ghebremariam Y, LePendu P, Lee J, 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
30. McColl K. Effect of Proton Pump Inhibitors on Vitamins and Iron. Am J Gastroenterol. 2009;104(S2):S5-S9. doi:10.1038/ajg.2009.45
31. Toh J, Ong E, Wilson R. Hypomagnesaemia associated with long-term use of proton pump inhibitors. Gastroenterol Rep (Oxf). 2014;3(3): 243-53. doi:10.1093/gastro/gou054
32. Dial M. Proton Pump Inhibitor Use and Enteric Infections. Am J Gastroenterol. 2009;104(S2):S10-S16. doi:10.1038/ajg.2009.46
33. Eom C, Jeon C, Lim J, Cho E, Park S, Lee K. Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis. Can Med Assoc J. 2010;183(3):310-9. doi:10.1503/cmaj.092129
34. Bosch J, Eikelboom J, Connolly S, et al. Rationale, Design and Baseline Characteristics of Participants in the C ardiovascular O utco m es for P eople Using A nticoagulation S trategie s (COMPASS) Trial. Canadian J Cardiol. 2017;33(8):1027-35. doi:10.1016/j.cjca. 2017.06.001

________________________________________________

1. Valgimigli M, Bueno H, Byrne R, et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. Europ J Cardio-Thoracic Surgery. 2017;53(1):34-78. doi:10.1093/ejcts/ezx334
2. Steffel J, Verhamme P, Potpara T, 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):1330-193. doi:10.1093/eurheartj/ehy136
3. Harjai K, Shenoy C, Orshaw P, Usmani S, Boura J, Mehta R. Clinical Outcomes in Patients With the Concomitant Use of Clopidogrel and Proton Pump Inhibitors After Percutaneous Coronary Intervention: An Analysis From the Guthrie Health Off-Label Stent (GHOST) Investigators. Circulation: Cardiovascular Interventions. 2011;4(2):162-70. doi:10.1161/circinterventions.110.958884
4. Juurlink D, Gomes T, Ko D, et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. Can Med Assoc J. 2009;180(7):713-18. doi:10.1503/cmaj.082001
5. Schmidt M, Johansen M, Robertson D, et al. Concomitant use of clopidogrel and proton pump inhibitors is not associated with major adverse cardiovascular events following coronary stent implantation. Aliment Pharmacol Ther. 2011;35(1):165-74. doi:10.1111/j.1365-2036.2011. 04890.x
6. Simon T, Steg P, Gilard M, et al. Clinical Events as a Function of Proton Pump Inhibitor Use, Clopidogrel Use, and Cytochrome P450 2C19 Genotype in a Large Nationwide Cohort of Acute Myocardial Infarction: Results From the French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) Registry. Circulation. 2011;123(5):474-82. doi:10.1161/circulationaha.110.965640
7. van Boxel O, van Oijen M, Hagenaars M, Smout A, Siersema P. Cardiovascular and Gastrointestinal Outcomes in Clopidogrel Users on Proton Pump Inhibitors: Results of a Large Dutch Cohort Study. Am J Gastroenterol. 2010;105(11):2430-36. doi:10.1038/ajg.2010.334
8. Charlot M, Ahlehoff O, Jorgensen C, et al. Proton pump inhibitors are associated with cardiovascular risk independent of clopidogrel use in patients with myocardial infarction: a nationwide propensity score matched study. J Am Coll Cardiol. 2010;55(10):A108.E1005. doi:10.1016/s0735-1097(10)61006-6
9. Schmidt M, Johansen M, Robertson D, et al. Concomitant use of clopidogrel and proton pump inhibitors is not associated with major adverse cardiovascular events following coronary stent implantation. Aliment Pharmacol Ther. 2011;35(1):165-74. doi:10.1111/j.1365-2036.2011. 04890.x
10. Valkhoff V,‘t Jong G, Van Soest E, Kuipers E, Sturkenboom M. Risk of recurrent myocardial infarction with the concomitant use of clopidogrel and proton pump inhibitors. Aliment Pharmacol Ther. 2010;33(1):77-88. doi:10.1111/j.1365-2036.2010.04485.x
11. Cardoso R, Benjo A, DiNicolantonio J, et al. Incidence of cardiovascular events and gastrointestinal bleeding in patients receiving clopidogrel with and without proton pump inhibitors: an updated meta-analysis. Open Heart. 2015;2(1):e000248. doi:10.1136/openhrt-2015-000248
12. Wedemeyer R, Blume H. Pharmacokinetic Drug Interaction Profiles of Proton Pump Inhibitors: An Update. Drug Saf. 2014;37(4):201-11. doi:10.1007/s40264-014-0144-0
13. Angiolillo D, Gibson C, Cheng S, et al. Differential Effects of Omeprazole and Pantoprazole on the Pharmacodynamics and Pharmacokinetics of Clopidogrel in Healthy Subjects: Randomized, Placebo-Controlled, Crossover Comparison Studies. Clinical Pharmacology & Therapeutics. 2010;89(1):65-74. doi:10.1038/clpt.2010.219
14. Hokimoto S, Mizobe M, Akasaka T, et al. Impact of CYP2C19 Polymorphism and Proton Pump Inhibitors on Platelet Reactivity to Clopidogrel and Clinical Outcomes Following Stent Implantation. Thromb Res. 2014;133(4):599-605. doi:10.1016/j.thromres.2014.01.003
15. Frelinger A, Lee R, Mulford D, et al. A Randomized, 2-Period, Crossover Design Study to Assess the Effects of Dexlansoprazole, Lansoprazole, Esomeprazole, and Omeprazole on the Steady-State Pharmacokinetics and Pharmacodynamics of Clopidogrel in Healthy Volunteers. J Am Coll Cardiol. 2012;59(14):1304-11. doi:10.1016/j. jacc.2011.12.024
16. Information for Healthcare Professionals: Update to the labeling of Clopidogrel Bisulfate (marketed as Plavix) to alert healthcare professionals about a drug interaction with omeprazole (marketed as Prilosec and Prilosec OTC) [Ссылка доступна на 23.05.2018];2009 http://www.pdr.net/fda-drug-safety-communication/plavix?druglabelid= 525&id=5033
17. Sherwood MW, Melloni C, Jones WS, et al. Individual proton pump inhibitors and outcomes in patients with coronary artery disease on dual antiplatelet therapy: a systematic review. J Am Heart Assoc. 2015;4(11):e002245. doi: 10.1161/JAHA.115.002245
18. Pello Lázaro A, Cristóbal C, Franco-Peláez J, et al. Use of Proton-Pump Inhibitors Predicts Heart Failure and Death in Patients with Coronary Artery Disease. PLoS ONE. 2017;12(1):e0169826. doi:10. 1371/journal.pone.0169826
19. Bhatt DL, Cryer BL, Contant CF, et al. Clopidogrel with or without Omeprazole in Coronary Disease. New England J Medicine. 2011; 364(7):681-83. doi:10.1056/nejmc1013859
20. Hsu P, Lai K, Liu C. Esomeprazole With Clopidogrel Reduces Peptic Ulcer Recurrence, Compared With Clopidogrel Alone, in Patients With Atherosclerosis. Gastroenterology. 2011;140(3):791-8.e2. doi:10.1053/j.gastro.2010.11.056
21. Hsu P. Proton Pump Inhibitor Prevents Clinically Significant Upper Gastrointestinal Evetns in Clopidogrel Users With Ulcer History. Gastroenterology. 2012;142(5):S-27. doi:10.1016/s0016-5085(12)60109-7
22. Vaduganathan M, Cannon C, Cryer B, et al. Efficacy and Safety of Proton-Pump Inhibitors in High-Risk Cardiovascular Subsets of the COGENT Trial. Am J Med. 2016;129(9):1002-5. doi:10.1016/j.amjmed. 2016.03.042
23. Bhurke S, Martin B, Li C, Franks A, Bursac Z, Said Q. Effect of the Clopidogrel-Proton Pump Inhibitor Drug Interaction on Adverse Cardiovascular Events in Patients with Acute Coronary Syndrome. Pharmacotherapy: J Human Pharmacology and Drug Therapy. 2012; 32(9):809-18. doi:10.1002/j.1875-9114.2012.01112.x
24. Chandrasekhar J, Bansilal S, Baber U, et al. Impact of proton pump inhibitors and dual antiplatelet therapy cessation on outcomes following percutaneous coronary intervention: Results From the PARIS Registry. Catheterization and Cardiovascular Interventions. 2016;89(7):E217-E225. doi:10.1002/ccd.26716
25. [Komarov A.L. Factors determining the prognosis and effectiveness of antiplatelet therapy in patients with chronic ischemic heart disease. Thesis for a doctor of medicsl sciences degree M., 2013 (In Russ.)]. Available at: http://cardioweb.ru/files/autoref/%D0%B0%D0%B2%D1%82%D0%BE%D1%80%D0%B5%D1%84%D0%B5% D1% 80% D0% B0% D1% 82% 20% D0% B4% D0% BC% D0% BD% 20% D0% 9A% D0% BE% D0% BC% D0% B0% D1% 80% D0% BE% D0% B2% 20% D0% 90.% D0% 9B..pdf. The link is active on May 23, 2018
26. Sukhovershin RA, Cooke JP. How may proton pump inhibitors impair cardiovascular health? Amer J Cardiovascular drugs : drugs, devices, and other interventions. 2016;16(3):153-61. doi:10.1007/s40256-016-0160-9
27. Goodman S, Clare R, Pieper K, et al. Association of Proton Pump Inhibitor Use on Cardiovascular Outcomes With Clopidogrel and Ticagrelor: Insights From the Platelet Inhibition and Patient Outcomes Trial. Circulation. 2012;125(8):978-86. doi:10.1161/circulationaha.111. 032912
28. Shah N, LePendu P, Bauer-Mehren A, et al. Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population. PLoS ONE. 2015;10(6):e0124653. doi:10.1371/journal.pone.0124653
29. Ghebremariam Y, LePendu P, Lee J, 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
30. McColl K. Effect of Proton Pump Inhibitors on Vitamins and Iron. Am J Gastroenterol. 2009;104(S2):S5-S9. doi:10.1038/ajg.2009.45
31. Toh J, Ong E, Wilson R. Hypomagnesaemia associated with long-term use of proton pump inhibitors. Gastroenterol Rep (Oxf). 2014;3(3): 243-53. doi:10.1093/gastro/gou054
32. Dial M. Proton Pump Inhibitor Use and Enteric Infections. Am J Gastroenterol. 2009;104(S2):S10-S16. doi:10.1038/ajg.2009.46
33. Eom C, Jeon C, Lim J, Cho E, Park S, Lee K. Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis. Can Med Assoc J. 2010;183(3):310-9. doi:10.1503/cmaj.092129
34. Bosch J, Eikelboom J, Connolly S, et al. Rationale, Design and Baseline Characteristics of Participants in the C ardiovascular O utco m es for P eople Using A nticoagulation S trategie s (COMPASS) Trial. Canadian J Cardiol. 2017;33(8):1027-35. doi:10.1016/j.cjca. 2017.06.001

Авторы

А.Л. КОМАРОВ 1, О.О. ШАХМАТОВА 1, В. МУРАСЕЕВА 1, Е.С. НОВИКОВА 1, Е.В. ГУСЬКОВА 2, Е.П. ПАНЧЕНКО 1

1 Отдел клинических проблем атеротромбоза ФГБУ «Национальный медицинский исследовательский центр кардиологии» Минздрава России, Москва, Россия;
2 ФГБУ «Национальный медико-хирургический центр им. Н.И. Пирогова» Минздрава России, Москва, Россия

________________________________________________

A.L. KOMAROV 1, O.O. SHAKHMATOVA 1, V. MURASEEVA 1, E.S. NOVIKOVA 1, E.V. GUSKOVA 2, E.P. PANCHENKO 1

1 Department of Clinical Problems of Atherothrombosis of the National Medical Research Center for Cardiology, Moscow, Russia
1 Pirogov National Medical and Surgical Center, Moscow, Russia

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