Применение блокаторов ренин-ангиотензиновой системы у пациентов с COVID-19

Родионов А.В. Применение блокаторов ренин-ангиотензиновой системы у пациентов с COVID-19. Consilium Medicum. 2021; 23 (10): 760–764. DOI: 10.26442/20751753.2021.10.201139

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Rodionov AV. The use of renin-angiotensin system blockers in patients with COVID-19. Consilium Medicum. 2021; 23 (10): 760–764. DOI:10.26442/20751753.2021.10.201139

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Аннотация

Пандемия COVID-19 ставит перед врачами много вопросов, связанных с лечением как самого коронавирусного заболевания, так и сопутствующей патологии. Известно, что возбудитель SARS-CoV‑2 проникает в организм через рецептор ангиотензинпревращающего фермента (АПФ)-2, в связи с чем возникает вопрос о допустимости применения блокаторов ренин-ангиотензиновой системы (РАС), в том числе ингибиторов АПФ у этих пациентов. Многочисленные когортные исследования, единичные рандомизированные контролируемые исследования и их метаанализы продемонстрировали безопасность применения блокаторов РАС у пациентов с COVID-19 в сочетании с сохранением их органопротективного действия. Остается неясным, оказывают ли эти препараты собственное благоприятное влияние на течение COVID-19. Выбор конкретного блокатора РАС у пациентов с коронавирусной инфекцией и сопутствующими сердечно-сосудистыми заболеваниями должен основываться на фармакокинетических и фармакодинамических свойствах препаратов, анализе сочетанной патологии и оценке возможных лекарственных взаимодействий.

Ключевые слова: COVID-19, ингибиторы ангиотензинпревращающего фермента, артериальная гипертензия

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The COVID-19 pandemic poses a lot of questions for doctors regarding the treatment of both the coronavirus disease itself and the comorbidities. It is known that SARS-CoV-2 enters the cells through the angiotensin-converting enzyme (ACE)-2 receptor, which raises the question about permissibility of the use of renin-angiotensin system (RAS) blockers, and specifically ACE inhibitors, in these patients. Numerous cohort studies, single randomized controlled trials and their meta-analyzes have demonstrated the safety of the use of RAS blockers in COVID-19 patients, as well as their organoprotective effect. It remains unclear whether these drugs have their own beneficial effect on the course of COVID-19. The selection of a particular RAS blocker in patients with coronavirus infection and cardiovascular comorbidities should be based on the pharmacokinetic and pharmacodynamic features of the drugs, as well as the analysis of comorbidity and the assessment of possible drug interactions.

Keywords: COVID-19, angiotensin-converting enzyme inhibitors, arterial hypertension

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Список литературы

1. The European Society for Cardiology. ESC Guidance for the Diagnosis and Management of CV Disease during the COVID-19 Pandemic. Available at: https://www.escardio.org/Education/COVID-19-and-Cardiology/ESC-COVID-19-Guidance. Accessed: 17.09.2021.
2. Davidson AM, Wysocki J, Batlle D. Interaction of SARS-CoV-2 and Other Coronavirus With ACE (Angiotensin-Converting Enzyme)-2 as Their Main Receptor: Therapeutic Implications. Hypertension. 2020;76(5):1339-49. DOI:10.1161/HYPERTENSIONAHA.120.15256
3. Sommerstein R, Gråni C. Rapid response: preventing a Covid-19 pandemic: ACE inhibitors as a potential risk factor for fatal Covid19. BMJ. 2020;368:m810. DOI:10.1136/bmj.m810
4. Kai H, Kai M. Interactions of coronaviruses with ACE2, angiotensin II, and RAS inhibitors – lessons from available evidence and insights into COVID-19. Hypertens Res. 2020;43(7):648-54. DOI:10.1038/s41440-020-0455-8
5. Reus P, Schneider A-K, Ulshöfer T, et al. Characterization of ACE Inhibitors and AT1R Antagonists with Regard to Their Effect on ACE2 Expression and Infection with SARS-CoV-2 Using a Caco-2 Cell Model. Life. 2021;11(8):810. DOI:10.3390/life11080810
6. Zhang P, Zhu L, Cai J, et al. Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19. Circ Res. 2020;126(12):1671-81. DOI:10.1161/CIRCRESAHA.120.317134
7. Lopes RD, Macedo AVS, de Barros E Silva PGM, et al. Effect of Discontinuing vs Continuing Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on Days Alive and Out of the Hospital in Patients Admitted With COVID-19: A Randomized Clinical Trial. JAMA. 2021;325(3):254-64. DOI:10.1001/jama.2020.25864
8. Mancia G, Rea F, Ludergnani M, Apolone G, Corrao G. Renin-angiotensin-aldosterone system blockers and the risk of Covid-19. N Engl J Med. 2020;382:2431-40.
9. Reynolds HR, Adhikari S, Pulgarin C, et al. Renin–angiotensin–aldosterone system inhibitors and risk of Covid-19. N Engl J Med. 2020;382:2441-8.
10. Meng J, Xiao G, Zhang J, et al. Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension. Emerg Microbes Infect. 2020;9(1):757-60. DOI:10.1080/22221751.2020.1746200
11. Li J, Wang X, Chen J, et al. Association of Renin-Angiotensin System Inhibitors With Severity or Risk of Death in Patients With Hypertension Hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China. JAMA Cardiol. 2020;5(7):825-30. DOI:10.1001/jamacardio.2020.1624
12. Wang Z, Zhang D, Wang S, et al. A Retrospective Study from 2 Centers in China on the Effects of Continued Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Patients with Hypertension and COVID-19. Med Sci Monit. 2020;26:e926651. DOI:10.12659/MSM.926651
13. Bean DM, Kraljevic Z, Searle T, et al. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are not associated with severe COVID-19 infection in a multi-site UK acute hospital trust. Eur J Heart Fail. 2020;22(6):967-74. DOI:10.1002/ejhf.1924
14. Baral R, Tsampasian V, Debski M, et al. Association Between Renin-Angiotensin-Aldosterone System Inhibitors and Clinical Outcomes in Patients With COVID-19: A Systematic Review and Meta-analysis. JAMA Netw Open. 2021;4(3):e213594. DOI:10.1001/jamanetworkopen.2021.3594
15. Jia N, Zhang G, Sun X, et al. Influence of angiotensin converting enzyme inhibitors/angiotensin receptor blockers on the risk of all-cause mortality and other clinical outcomes in patients with confirmed COVID-19: A systemic review and meta-analysis. J Clin Hypertens (Greenwich). 2021;10.1111/jch.14329. DOI:10.1111/jch.14329
16. Fernando ME, Drovandi A, Golledge J. Meta-analysis of the association between angiotensin pathway inhibitors and COVID-19 severity and mortality. Syst Rev. 2021;10(1):243. DOI:10.1186/s13643-021-01802-6
17. Núñez-Gil IJ, Olier I, Feltes G, et al. HOPE COVID-19 Investigators (Cols Appendix). Renin-angiotensin system inhibitors effect before and during hospitalization in COVID-19 outcomes: Final analysis of the international HOPE COVID-19 (Health Outcome Predictive Evaluation for COVID-19) registry. Am Heart J. 2021;237:104-15. DOI:10.1016/j.ahj.2021.04.001
18. Hockham C, Kotwal S, Wilcox A, et al. CLARITY Investigators. Protocol for the Controlled evaLuation of Angiotensin Receptor blockers for COVID-19 respIraTorY disease (CLARITY): a randomised controlled trial. Trials. 2021;22(1):573. DOI:10.1186/s13063-021-05521-0
19. Satsangi S, Gupta N, Kodan P. Current and New Drugs for COVID-19 Treatment and Its Effects on the Liver. J Clin Transl Hepatol. 2021;9(3):436-46. DOI:10.14218/JCTH.2020.00174
20. Song JC, White CM. Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update. Clin Pharmacokinet. 2002;41(3):207-24. DOI:10.2165/00003088-200241030-00005
21. Hayes PC, Plevris JN, Bouchier IA. Pharmacokinetics of enalapril and lisinopril in subjects with normal and impaired hepatic function. J Hum Hypertens. 1989;3(Suppl. 1):153-8.
22. Михеева О.М., Дроздов В.Н., Комиссаренко И.А. Фармакокинетические и фармакодинамические особенности антигипертензивных препаратов при лечении больных артериальной гипертонией в сочетании с хроническими заболеваниями печени. Терапевтический архив. 2011;83(12):49-55 [Mikheeva OM, Drozdov VN, Komissarenko IA. Pharmacokinetic and pharmacodynamic characteristics of antihypertensive drugs in the treatment of hypertensive patients with chronic diseases of the liver. Terapevticheskii Arkhiv (Ter. Arkh.). 2011;83(12):49-55 (in Russian)].
23. Лазебник Л.Б., Комиссаренко И.А., Михеева О.М., и др. Комбинированная терапия артериальной гипертонии в сочетании с патологией печени. Место ингибиторов ангиотензинпревращающего фермента. Кардиология. 2009;49(3):28-33 [Lazebnik LB, Komissarenko IA, Mikheeva OM, et al. Combination therapy of arterial hypertension combined with liver pathology. The place of angiotensin converting enzyme inhibitors. Kardiologiia. 2009;49(3):28-33 (in Russian)].
24. Neal DA, Brown MJ, Wilkinson IB, et al. Hemodynamic effects of amlodipine, bisoprolol, and lisinopril in hypertensive patients after liver transplantation. Transplantation. 2004;77(5):748-50. DOI:10.1097/01.tp.0000116418.78963.dc
25. Williams B, Mancia G, Spiering W, et al. ESC Scientific Document Group. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021-104. DOI:10.1093/eurheartj/ehy339

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1. The European Society for Cardiology. ESC Guidance for the Diagnosis and Management of CV Disease during the COVID-19 Pandemic. Available at: https://www.escardio.org/Education/COVID-19-and-Cardiology/ESC-COVID-19-Guidance. Accessed: 17.09.2021.
2. Davidson AM, Wysocki J, Batlle D. Interaction of SARS-CoV-2 and Other Coronavirus With ACE (Angiotensin-Converting Enzyme)-2 as Their Main Receptor: Therapeutic Implications. Hypertension. 2020;76(5):1339-49. DOI:10.1161/HYPERTENSIONAHA.120.15256
3. Sommerstein R, Gråni C. Rapid response: preventing a Covid-19 pandemic: ACE inhibitors as a potential risk factor for fatal Covid19. BMJ. 2020;368:m810. DOI:10.1136/bmj.m810
4. Kai H, Kai M. Interactions of coronaviruses with ACE2, angiotensin II, and RAS inhibitors – lessons from available evidence and insights into COVID-19. Hypertens Res. 2020;43(7):648-54. DOI:10.1038/s41440-020-0455-8
5. Reus P, Schneider A-K, Ulshöfer T, et al. Characterization of ACE Inhibitors and AT1R Antagonists with Regard to Their Effect on ACE2 Expression and Infection with SARS-CoV-2 Using a Caco-2 Cell Model. Life. 2021;11(8):810. DOI:10.3390/life11080810
6. Zhang P, Zhu L, Cai J, et al. Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19. Circ Res. 2020;126(12):1671-81. DOI:10.1161/CIRCRESAHA.120.317134
7. Lopes RD, Macedo AVS, de Barros E Silva PGM, et al. Effect of Discontinuing vs Continuing Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on Days Alive and Out of the Hospital in Patients Admitted With COVID-19: A Randomized Clinical Trial. JAMA. 2021;325(3):254-64. DOI:10.1001/jama.2020.25864
8. Mancia G, Rea F, Ludergnani M, Apolone G, Corrao G. Renin-angiotensin-aldosterone system blockers and the risk of Covid-19. N Engl J Med. 2020;382:2431-40.
9. Reynolds HR, Adhikari S, Pulgarin C, et al. Renin–angiotensin–aldosterone system inhibitors and risk of Covid-19. N Engl J Med. 2020;382:2441-8.
10. Meng J, Xiao G, Zhang J, et al. Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension. Emerg Microbes Infect. 2020;9(1):757-60. DOI:10.1080/22221751.2020.1746200
11. Li J, Wang X, Chen J, et al. Association of Renin-Angiotensin System Inhibitors With Severity or Risk of Death in Patients With Hypertension Hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China. JAMA Cardiol. 2020;5(7):825-30. DOI:10.1001/jamacardio.2020.1624
12. Wang Z, Zhang D, Wang S, et al. A Retrospective Study from 2 Centers in China on the Effects of Continued Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Patients with Hypertension and COVID-19. Med Sci Monit. 2020;26:e926651. DOI:10.12659/MSM.926651
13. Bean DM, Kraljevic Z, Searle T, et al. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are not associated with severe COVID-19 infection in a multi-site UK acute hospital trust. Eur J Heart Fail. 2020;22(6):967-74. DOI:10.1002/ejhf.1924
14. Baral R, Tsampasian V, Debski M, et al. Association Between Renin-Angiotensin-Aldosterone System Inhibitors and Clinical Outcomes in Patients With COVID-19: A Systematic Review and Meta-analysis. JAMA Netw Open. 2021;4(3):e213594. DOI:10.1001/jamanetworkopen.2021.3594
15. Jia N, Zhang G, Sun X, et al. Influence of angiotensin converting enzyme inhibitors/angiotensin receptor blockers on the risk of all-cause mortality and other clinical outcomes in patients with confirmed COVID-19: A systemic review and meta-analysis. J Clin Hypertens (Greenwich). 2021;10.1111/jch.14329. DOI:10.1111/jch.14329
16. Fernando ME, Drovandi A, Golledge J. Meta-analysis of the association between angiotensin pathway inhibitors and COVID-19 severity and mortality. Syst Rev. 2021;10(1):243. DOI:10.1186/s13643-021-01802-6
17. Núñez-Gil IJ, Olier I, Feltes G, et al. HOPE COVID-19 Investigators (Cols Appendix). Renin-angiotensin system inhibitors effect before and during hospitalization in COVID-19 outcomes: Final analysis of the international HOPE COVID-19 (Health Outcome Predictive Evaluation for COVID-19) registry. Am Heart J. 2021;237:104-15. DOI:10.1016/j.ahj.2021.04.001
18. Hockham C, Kotwal S, Wilcox A, et al. CLARITY Investigators. Protocol for the Controlled evaLuation of Angiotensin Receptor blockers for COVID-19 respIraTorY disease (CLARITY): a randomised controlled trial. Trials. 2021;22(1):573. DOI:10.1186/s13063-021-05521-0
19. Satsangi S, Gupta N, Kodan P. Current and New Drugs for COVID-19 Treatment and Its Effects on the Liver. J Clin Transl Hepatol. 2021;9(3):436-46. DOI:10.14218/JCTH.2020.00174
20. Song JC, White CM. Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update. Clin Pharmacokinet. 2002;41(3):207-24. DOI:10.2165/00003088-200241030-00005
21. Hayes PC, Plevris JN, Bouchier IA. Pharmacokinetics of enalapril and lisinopril in subjects with normal and impaired hepatic function. J Hum Hypertens. 1989;3(Suppl. 1):153-8.
22. Mikheeva OM, Drozdov VN, Komissarenko IA. Pharmacokinetic and pharmacodynamic characteristics of antihypertensive drugs in the treatment of hypertensive patients with chronic diseases of the liver. Terapevticheskii Arkhiv (Ter. Arkh.). 2011;83(12):49-55 (in Russian).
23. Lazebnik LB, Komissarenko IA, Mikheeva OM, et al. Combination therapy of arterial hypertension combined with liver pathology. The place of angiotensin converting enzyme inhibitors. Kardiologiia. 2009;49(3):28-33 (in Russian).
24. Neal DA, Brown MJ, Wilkinson IB, et al. Hemodynamic effects of amlodipine, bisoprolol, and lisinopril in hypertensive patients after liver transplantation. Transplantation. 2004;77(5):748-50. DOI:10.1097/01.tp.0000116418.78963.dc
25. Williams B, Mancia G, Spiering W, et al. ESC Scientific Document Group. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021-104. DOI:10.1093/eurheartj/ehy339

Авторы

А.В. Родионов*

ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия
*rodionov_a_v_1@staff.sechenov.ru

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Anton V. Rodionov*

Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
*rodionov_a_v_1@staff.sechenov.ru

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