Skip to main content
Top
Published in: Clinical Hypertension 1/2020

Open Access 01-12-2020 | COVID-19 | Review

Is the use of RAS inhibitors safe in the current era of COVID-19 pandemic?

Authors: Sungha Park, Hae Young Lee, Eun Joo Cho, Ki Chul Sung, Juhan Kim, Dae-Hee Kim, Sang-Hyun Ihm, Kwang-il Kim, Il-Suk Sohn, Wook-Jin Chung, Hyeon Chang Kim, Sung Kee Ryu, Wook Bum Pyun, Jinho Shin, on behalf of the Korean Society of Hypertension

Published in: Clinical Hypertension | Issue 1/2020

Login to get access

Abstract

Antihypertensive drugs are one of the most widely used pharmacologic agent in the world and it is predominantly used in the elderly subjects. Pneumonia is the most common cause of death in the extremely old subject. During infection and its complication such as sepsis, hypotension could be exacerbated by antihypertensive drugs because homeostasis mechanisms such as sodium balance, renin angiotensin aldosterone system and/or sympathetic nervous system can be mitigated by antihypertensive drug therapy. Severe Acute Respiratory Syndrome-Coronavirus-1 and 2 viral surface protein is known to attach angiotensin converting enzyme 2 (ACE2) on the cell membrane to facilitate viral entry into the cytoplasm. Despite the theoretical concerns of increased ACE2 expression by Renin-Angiotensin-Aldosterone system (RAS) blockade, there is no evidence that RAS inhibitors are harmful during COVID-19 infection and have in fact been shown to be beneficial in animal studies. Therefore, it is recommended to maintain RAS blockade during the current corona virus pandemic.
Literature
1.
go back to reference Hsu WT, Galm BP, Schrank G, Hsu TC, Lee SH, Park JY, et al. Effect of renin-angiotensin-aldosterone system inhibitors on short-term mortality after Sepsis: a population-based cohort study. Hypertension. 2020;75:483–91.CrossRef Hsu WT, Galm BP, Schrank G, Hsu TC, Lee SH, Park JY, et al. Effect of renin-angiotensin-aldosterone system inhibitors on short-term mortality after Sepsis: a population-based cohort study. Hypertension. 2020;75:483–91.CrossRef
2.
go back to reference Hsu CT, Tai HC, Chung JY, Chen JH, Chen WL. Depressed sympathovagal modulation indicates sepsis in patients with suspected infection. Medicine (Baltimore). 2020;99:e18961.CrossRef Hsu CT, Tai HC, Chung JY, Chen JH, Chen WL. Depressed sympathovagal modulation indicates sepsis in patients with suspected infection. Medicine (Baltimore). 2020;99:e18961.CrossRef
3.
go back to reference Gilstrap LG, Fonarow GC, Desai AS, Liang L, Matsouaka R, DeVore AD, et al. Initiation, continuation, or withdrawal of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and outcomes in patients hospitalized with heart failure with reduced ejection fraction. J Am Heart Assoc. 2017;6. Gilstrap LG, Fonarow GC, Desai AS, Liang L, Matsouaka R, DeVore AD, et al. Initiation, continuation, or withdrawal of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and outcomes in patients hospitalized with heart failure with reduced ejection fraction. J Am Heart Assoc. 2017;6.
4.
go back to reference Prins KW, Neill JM, Tyler JO, Eckman PM, Duval S. Effects of Beta-blocker withdrawal in acute decompensated heart failure: a systematic review and meta-analysis. JACC Heart Fail. 2015;3:647–53.CrossRef Prins KW, Neill JM, Tyler JO, Eckman PM, Duval S. Effects of Beta-blocker withdrawal in acute decompensated heart failure: a systematic review and meta-analysis. JACC Heart Fail. 2015;3:647–53.CrossRef
5.
go back to reference Ohkubo T, Chapman N, Neal B, Woodward M, Omae T, Chalmers J, et al. Effects of an angiotensin-converting enzyme inhibitor-based regimen on pneumonia risk. Am J Respir Crit Care Med. 2004;169:1041–5.CrossRef Ohkubo T, Chapman N, Neal B, Woodward M, Omae T, Chalmers J, et al. Effects of an angiotensin-converting enzyme inhibitor-based regimen on pneumonia risk. Am J Respir Crit Care Med. 2004;169:1041–5.CrossRef
6.
go back to reference Lee JH, Kim MS, Yoo BS, Park SJ, Park JJ, Shin MS, et al. KSHF guidelines for the Management of Acute Heart Failure: part II. Treatment of Acute Heart Failure. Korean Circ J. 2019;49:22–45.CrossRef Lee JH, Kim MS, Yoo BS, Park SJ, Park JJ, Shin MS, et al. KSHF guidelines for the Management of Acute Heart Failure: part II. Treatment of Acute Heart Failure. Korean Circ J. 2019;49:22–45.CrossRef
7.
go back to reference British Infection S, British Thoracic S, Health Protection A. Pandemic flu: clinical management of patients with an influenza-like illness during an influenza pandemic. Provisional guidelines from the British Infection Society, British Thoracic Society, and Health Protection Agency in collaboration with the Department of Health. Thorax 2007;62 Suppl 1:1–46. British Infection S, British Thoracic S, Health Protection A. Pandemic flu: clinical management of patients with an influenza-like illness during an influenza pandemic. Provisional guidelines from the British Infection Society, British Thoracic Society, and Health Protection Agency in collaboration with the Department of Health. Thorax 2007;62 Suppl 1:1–46.
8.
go back to reference Arendse LB, Danser AHJ, Poglitsch M, Touyz RM, Burnett JC Jr, Llorens-Cortes C, et al. Novel therapeutic approaches targeting the renin-angiotensin system and associated peptides in hypertension and heart failure. Pharmacol Rev. 2019;71:539–70.CrossRef Arendse LB, Danser AHJ, Poglitsch M, Touyz RM, Burnett JC Jr, Llorens-Cortes C, et al. Novel therapeutic approaches targeting the renin-angiotensin system and associated peptides in hypertension and heart failure. Pharmacol Rev. 2019;71:539–70.CrossRef
9.
go back to reference Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000;275:33238–43.CrossRef Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000;275:33238–43.CrossRef
10.
go back to reference Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020.
11.
go back to reference Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020.
12.
go back to reference Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203:631–7.CrossRef Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203:631–7.CrossRef
13.
go back to reference Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. 2005;11:875–9.CrossRef Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. 2005;11:875–9.CrossRef
14.
go back to reference Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367:1260–3.CrossRef Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367:1260–3.CrossRef
15.
go back to reference Zambelli V, Bellani G, Borsa R, Pozzi F, Grassi A, Scanziani M, et al. Angiotensin-(1-7) improves oxygenation, while reducing cellular infiltrate and fibrosis in experimental acute respiratory distress syndrome. Intensive Care Med Exp. 2015;3:44.CrossRef Zambelli V, Bellani G, Borsa R, Pozzi F, Grassi A, Scanziani M, et al. Angiotensin-(1-7) improves oxygenation, while reducing cellular infiltrate and fibrosis in experimental acute respiratory distress syndrome. Intensive Care Med Exp. 2015;3:44.CrossRef
16.
go back to reference Burrell LM, Risvanis J, Kubota E, Dean RG, MacDonald PS, Lu S, et al. Myocardial infarction increases ACE2 expression in rat and humans. Eur Heart J. 2005;26:369–75 discussion 22-4.CrossRef Burrell LM, Risvanis J, Kubota E, Dean RG, MacDonald PS, Lu S, et al. Myocardial infarction increases ACE2 expression in rat and humans. Eur Heart J. 2005;26:369–75 discussion 22-4.CrossRef
17.
go back to reference Walters TE, Kalman JM, Patel SK, Mearns M, Velkoska E, Burrell LM. Angiotensin converting enzyme 2 activity and human atrial fibrillation: increased plasma angiotensin converting enzyme 2 activity is associated with atrial fibrillation and more advanced left atrial structural remodelling. Europace. 2017;19:1280–7.PubMed Walters TE, Kalman JM, Patel SK, Mearns M, Velkoska E, Burrell LM. Angiotensin converting enzyme 2 activity and human atrial fibrillation: increased plasma angiotensin converting enzyme 2 activity is associated with atrial fibrillation and more advanced left atrial structural remodelling. Europace. 2017;19:1280–7.PubMed
18.
go back to reference Deshotels MR, Xia H, Sriramula S, Lazartigues E, Filipeanu CM. Angiotensin II mediates angiotensin converting enzyme type 2 internalization and degradation through an angiotensin II type I receptor-dependent mechanism. Hypertension. 2014;64:1368–75.CrossRef Deshotels MR, Xia H, Sriramula S, Lazartigues E, Filipeanu CM. Angiotensin II mediates angiotensin converting enzyme type 2 internalization and degradation through an angiotensin II type I receptor-dependent mechanism. Hypertension. 2014;64:1368–75.CrossRef
19.
go back to reference Heurich A, Hofmann-Winkler H, Gierer S, Liepold T, Jahn O, Pohlmann S. TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein. J Virol. 2014;88:1293–307.CrossRef Heurich A, Hofmann-Winkler H, Gierer S, Liepold T, Jahn O, Pohlmann S. TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein. J Virol. 2014;88:1293–307.CrossRef
20.
go back to reference Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005;436:112–6.CrossRef Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005;436:112–6.CrossRef
Metadata
Title
Is the use of RAS inhibitors safe in the current era of COVID-19 pandemic?
Authors
Sungha Park
Hae Young Lee
Eun Joo Cho
Ki Chul Sung
Juhan Kim
Dae-Hee Kim
Sang-Hyun Ihm
Kwang-il Kim
Il-Suk Sohn
Wook-Jin Chung
Hyeon Chang Kim
Sung Kee Ryu
Wook Bum Pyun
Jinho Shin
on behalf of the Korean Society of Hypertension
Publication date
01-12-2020

Other articles of this Issue 1/2020

Clinical Hypertension 1/2020 Go to the issue