Renin–Angiotensin–Aldosterone System Inhibitors in Patients with COVID-19: General Considerations and Clinical Implications
Initially reported in China at the end of 2019, the coronavirus pandemic has now reached an international scale with more than 1.5 million cases worldwide and more than eighty thousands deaths by April 8th of this year. Recent studies have shown that the virus invades host cells by the angiotensin-converting enzyme 2 receptor, making it essential to viral transmission. Concerns have been raised about possible benefits and harms associated with the use of ACE inhibitors and angiotensin receptors blockers in these patients. However, there is lack of evidence to recommend even temporarily discontinuing renin-angiotensin system inhibitors/blockers in patients infected with the SARS-CoV-2.
Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis. 2020;20(5):533-4.https://doi.org/10.1016/S1473-3099(20)30120-1
Clerkin KJ, Fried JA, Raikhelkar J, Sayer G, Griffin JM, Masoumi A, et al. COVID-19 and cardiovascular disease. Circulation. 2020;141(20):1648-55. https://doi.org/10.1161/CIRCULATIONAHA.120.046941
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 Cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271-80. https://doi.org/10.1016/j.cell.2020.02.052
Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O. Potential effects of coronaviruses on the cardiovascular system: A review. JAMA Cardiol. Published online March 27, 2020. https://doi.org/10.1001/jamacardio.2020.1286
Zheng Y-Y, Ma Y-T, Zhang J-Y, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020;17(5):256-60. https://doi.org/10.1038/s41569-020-0360-5
Cohn JN, Johnson G, Ziesche S, Cobb F, Francis GS, Tristani F, et al. A comparison of enalapril with hydralazine–isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med. 1991;325(5):303-10. https://doi.org/10.1056/NEJM199108013250502
The Consensus Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure: results of the cooperative North Scandinavian enalapril survival study (CONSENSUS). N Engl J Med. 1987;316(23):1429-35. https://doi.org/10.1056/NEJM198706043162301
The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 1991;325(5):293-302. https://doi.org/10.1056/NEJM199108013250501
The SOLVD Investigators. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med. 1992;327(10):685-91. https://doi.org/10.1056/NEJM199209033271003
Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med. 1999;341(10):709-17. https://doi.org/10.1056/NEJM199909023411001
Pitt B, Remme WJ, Zannad F, Neaton J, Martinez F, Roniker B, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348(14):1309-21. https://doi.org/10.1056/NEJMoa030207
Kuhn JH, Li W, Choe H, Farzan M. What’s new in the renin–angiotensin system? Angiotensin-converting enzyme 2: a functional receptor for SARS coronavirus. CMLS, Cell Mol Life Sci. 2004;61(21):2738-43. https://doi.org/10.1007/s00018-004-4242-5
Meng J, Xiao G, Zhang J, He X, Ou M, Bi 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. https://doi.org/10.1080/22221751.2020.1746200
Liu Y, Yang Y, Zhang C, Huang F, Wang F, Yuan J, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci. 2020;63(3):364-74. https://doi.org/10.1007/s11427-020-1643-8
Epelman S, Shrestha K, Troughton RW, Francis GS, Sen S, Klein AL, et al. Soluble angiotensin-converting enzyme 2 in human heart failure: relation with myocardial function and clinical outcomes. J Card Fail. 2009;15(7):565-71. https://doi.org/10.1016/j.cardfail.2009.01.014
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. EP Europace. 2017;19(8):1280-7. https://doi.org/10.1093/europace/euw246
Ramchand J, Patel SK, Kearney LG, Matalanis G, Farouque O, Srivastava PM, et al. Plasma ACE2 activity predicts mortality in aortic stenosis and is associated with severe myocardial fibrosis. JACC Cardiovasc Imaging. 2020;13(3):655-64. https://doi.org/10.1016/j.jcmg.2019.09.005
Furuhashi M, Moniwa N, Mita T, Fuseya T, Ishimura S, Ohno K, et al. Urinary angiotensin-converting enzyme 2 in hypertensive patients may be increased by olmesartan, an angiotensin II receptor blocker. Am J Hypertens. 2015;28(1):15-21. https://doi.org/10.1093/ajh/hpu086
Guan W-J, Ni Z-Y, Hu Y, Liang W-H, Ou C-Q, He J-X, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708-20. https://doi.org/10.1056/NEJMoa2002032
Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. Published online March 13, 2020. https://doi.org/10.1001/jamainternmed.2020.0994
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;395(10229):1054-62. https://doi.org/10.1016/S0140-6736(20)30566-3
Peng YD, Meng K, Guan HQ, Leng L, Zhu RR, Wang BY, et al. Clinical characteristics and outcomes of 112 cardiovascular disease patients infected by 2019-nCoV. Chin J Cardiol. 2020;48:E004. https://doi.org/10.3760/cma.j.cn112148-20200220-00105
Helmrich SP, Ragland DR, Leung RW, Paffenbarger Junior RS. Physical activity and reduced occurrence of non-insulin-dependent diabetes mellitus. N Engl J Med. 1991;325(3):147-52. https://doi.org/10.1056/NEJM199107183250302
Pfeffer MA, Braunwald E, Moyé LA, Basta L, Brown Junior EJ, Cuddy TE, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction — results of the survival and ventricular enlargement trial. N Engl J Med. 1992;327(10):669-77. https://doi.org/10.1056/NEJM199209033271001
Yancy CW, Jessup M, Bozkurt B, Butler J, Casey Junior DE, Drazner MH, et al. 2013 ACCF/AHA guideline for the management of heart failure: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62(16):e147-239. https://doi.org/10.1161/CIR.0b013e31829e8776
Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37(27):2129-200. Erratum for: Eur Heart J. 2018;39(14):1206. https://doi.org/10.1093/eurheartj/ehx158
Comitê Coordenador da Diretriz de Insuficiência Cardíaca. Diretriz Brasileira de Insuficiência Cardíaca Crônica e Aguda. Arq Bras Cardiol. 2018;111(3):436-539.
Halliday BP, Wassall R, Lota AS, Khalique Z, Gregson J, Newsome S, et al. Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial. Lancet. 2019;393(10166):61-73.https://doi.org/10.1016/S0140-6736(18)32484-X
Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13–115. https://doi.org/10.1161/HYP.0000000000000065
Williams B, Mancia G, Spiering W, Rosei EA, Azizi M, Burnier M, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension: The task force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). Eur Heart J. 2018;39(33):3021-104. Erratum for: Eur Heart J. 2019;40(5):475. https://doi.org/10.1093/eurheartj/ehy686
Malachias MVB, Souza WKSB, Plavnik FL, Rodrigues CIS, Brandão AA, Neves MFT, et al. 7ª Diretriz Brasileira de Hipertensão Arterial. Arq Bras Cardiol. 2016;107(3):1-83.
Corbo JM, Delellis TM, Hill LG, Rindfuss SL, Nashelsky J. ACE Inhibitors or ARBs to prevent CKD in patients with microalbuminuria. Am Fam Physician. 2016;94(8):652-3.
Copyright (c) 2020 Neiberg de Alcantara Lima, Pedro Yuri Paiva Lima, Ricardo Lessa de Castro Junior, Eric Martin Sieloff, Stela Maria Vitorino Sampaio
This work is licensed under a Creative Commons Attribution 4.0 International License.