Impact of ACEI/ARB on clinical outcomes in Chinese patients with COVID-19: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

HUANG Xurui ¹ , YUAN Qi ² , WANG Ningfu ¹ , ZHOU Liang ¹ , YE Xianhua ¹ ,  HUANG Jinyu ¹

1. Department of Cardiology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310000, P. R. China;
2. Institute of Mental Health in Singapore, 999002, Singapore;

Corresponding author：

HUANG Jinyu, Email: hjyuo@163.com

Keywords：

Corona virus disease 2019; ACEI/ARB; Meta-analysis; Systematic review; Cohort study

DOI：

10.7507/1672-2531.202111071

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To systematically review the impact of ACEI/ARB (angiotensin converting enzyme inhibitor/ angiotensin receptor antagonist) treatment on the clinical outcomes of Chinese patients with COVID-19 infections. Methods PubMed, EMbase, Web of Science, The Cochrane Library, CNKI, WanFang Data, and VIP databases were electronically searched to collect cohort studies on the impact of the treatment with ACEI/ARB on the clinical outcomes of Chinese patients with COVID-19 infections from January 2020 to January 2022. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of the included studies. Then, meta-analysis was performed using RevMan 5.3 software. Results A total of 17 cohort studies involving 4 912 subjects were included. The results of meta-analysis showed that patients who were prescribed ACEI/ARB had shorter hospital stays (SMD=−0.28, 95%CI −0.46 to −0.11, P=0.002) and a lower mortality rate (OR=0.47, 95%CI 0.36 to 0.62, P<0.000 01) than patients who did not take ACEI/ARB. Conclusion Current evidence shows that the use of ACEI/ARB drugs can improve the clinical prognosis of Chinese patients with COVID-19 infections. Due to the limited quality and quantity of the included studies, more high-quality studies are needed to verify the above conclusion.

Citation： HUANG Xurui, YUAN Qi, WANG Ningfu, ZHOU Liang, YE Xianhua, HUANG Jinyu. Impact of ACEI/ARB on clinical outcomes in Chinese patients with COVID-19: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2022, 22(4): 438-443. doi: 10.7507/1672-2531.202111071 Copy

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8.	Huang Z, Cao J, Yao Y, et al. The effect of RAS blockers on the clinical characteristics of COVID-19 patients with hypertension. Ann Transl Med, 2020, 8(7): 430.
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17.	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): 757-760.
18.	Yang G, Tan Z, Zhou L, et al. Effects of angiotensinⅡ receptor blockers and ace (angiotensin-converting enzyme) inhibitors on virus infection, inflammatory status, and clinical outcomes in patients with COVID-19 and hypertension: a single-center retrospective study. Hypertension, 2020, 76(1): 51-58.
19.	Huang L, Chen Z, Ni L, et al. Impact of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on the inflammatory response and viral clearance in COVID-19 patients. Front Cardiovasc Med, 2021, 8: 710946.
20.	Pan W, Zhang J, Wang M, et al. Clinical features of COVID-19 in patients with essential hypertension and the impacts of renin-angiotensin-aldosterone system inhibitors on the prognosis of COVID-19 patients. Hypertension, 2020, 76(3): 732-741.
21.	Meng X, Liu Y, Wei C, et al. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers improved the outcome of patients with severe COVID-19 and hypertension. Sci China Life Sci, 2021, 64(5): 836-839.
22.	Wang HY, Peng S, Ye Z, et al. Renin-angiotensin system inhibitor is associated with the reduced risk of all-cause mortality in COVID-19 among patients with/without hypertension. Front Med, 2021: 1-9.
23.	Zhang P, Zhu L, Cai J, et al. Association of inpatient use of angiotensin-converting enzyme inhibitors and angiotensinⅡ receptor blockers with mortality among patients with hypertension hospitalized with COVID-19. Circ Res, 2020, 126(12): 1671-1681.
24.	廖玉华, 程翔, 曾秋棠, 等. 湖北省新型冠状病毒肺炎疫情下心血管病治疗与管理专家建议. 临床心血管病杂志, 2020, 36(3): 201-203.
25.	Bozkurt B, Kovacs R, Harrington B. Joint HFSA/ACC/AHA statement addresses concerns re: using RAAS antagonists in COVID-19. J Card Fail, 2020, 26(5): 370.
26.	Wu C, Chen X, Cai Y, 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, 2020, 180(7): 934-943.
27.	Kreutz R, Algharably EAE, Azizi M, et al. Hypertension, the renin-angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19. Cardiovasc Res, 2020, 116(10): 1688-1699.
28.	Watkins J. Preventing a COVID-19 pandemic. BMJ, 2020, 368: m810.
29.	Ferrario CM, Jessup J, Gallagher PE, et al. Effects of renin-angiotensin system blockade on renal angiotensin-(1-7) forming enzymes and receptors. Kidney Int, 2005, 68(5): 2189-2196.
30.	Hamming I, van Goor H, Turner AJ, et al. Differential regulation of renal angiotensin-converting enzyme (ACE) and ACE2 during ACE inhibition and dietary sodium restriction in healthy rats. Exp Physiol, 2008, 93(5): 631-638.
31.	Furuhashi M, Moniwa N, Mita T, 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.
32.	Mariana CP, Ramona PA, Ioana BC, et al. Urinary angiotensin converting enzyme 2 is strongly related to urinary nephrin in type 2 diabetes patients. Int Urol Nephrol, 2016, 48(9): 1491-1497.
33.	Vuille-dit-Bille RN, Camargo SM, Emmenegger L, et al. Human intestine luminal ACE2 and amino acid transporter expression increased by ACE-inhibitors. Amino Acids, 2015, 47(4): 693-705.
34.	Imai Y, Kuba K, Rao S, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature, 2005, 436(7047): 112-116.
35.	Ferrario CM, Strawn WB. Role of the renin-angiotensin-aldosterone system and proinflammatory mediators in cardiovascular disease. Am J Cardiol, 2006, 98(1): 121-128.
36.	Huang F, Guo J, Zou Z, et al. Angiotensin II plasma levels are linked to disease severity and predict fatal outcomes in H7N9-infected patients. Nat Commun, 2014, 5: 3595.
37.	Pinter M, Kwanten WJ, Jain RK. Renin-angiotensin system inhibitors to mitigate cancer treatment-related adverse events. Clin Cancer Res, 2018, 24(16): 3803-3812.
38.	Hsu WT, Galm BP, Schrank G, et al. Effect of renin-angiotensin-aldosterone system inhibitors on short-term mortality after sepsis: a population-based cohort study. Hypertension, 2020, 75(2): 483-491.
39.	Henry C, Zaizafoun M, Stock E, et al. Impact of angiotensin-converting enzyme inhibitors and statins on viral pneumonia. Proc (Bayl Univ Med Cent), 2018, 31(4): 419-423.
40.	Vaduganathan M, Vardeny O, Michel T, et al. Renin-angiotensin-aldosterone system inhibitors in patients with COVID-19. N Engl J Med, 2020, 382(17): 1653-1659.
41.	Kai H, Kai M. Interactions of coronaviruses with ACE2, angiotensinⅡ, and RAS inhibitors-lessons from available evidence and insights into COVID-19. Hypertens Res, 2020, 43(7): 648-654.
42.	Gilstrap LG, Fonarow GC, Desai AS, 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(2): e004675.

1. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol, 2020, 5(4): 536-544.
2. Zheng YY, Ma YT, Zhang JY, et al. COVID-19 and the cardiovascular system. Nat Rev Cardiol, 2020, 17(5): 259-260.
3. Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection. Lancet Respir Med, 2020, 8(4): e21.
4. Chen J, Jiang Q, Xia X, et al. Individual variation of the SARS-CoV-2 receptor ACE2 gene expression and regulation. Aging Cell, 2020, 19(7): e13168.
5. 中华人民共和国国家卫生健康委员会. 新型冠状病毒肺炎诊疗方案(试行第八版). 中华临床感染病杂志, 2020, 13(5): 321-328.
6. Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions (version 5.1. 0). The Cochrane Collaboration, 2011. Available at: http://www.cochrane-handbook.org.
7. Tan ND, Qiu Y, Xing XB, et al. Associations between angiotensin-converting enzyme inhibitors and angiotensinⅡ receptor blocker use, gastrointestinal symptoms, and mortality among patients with COVID-19. Gastroenterology, 2020, 159(3): 1170-1172.
8. Huang Z, Cao J, Yao Y, et al. The effect of RAS blockers on the clinical characteristics of COVID-19 patients with hypertension. Ann Transl Med, 2020, 8(7): 430.
9. Zeng Z, Sha T, Zhang Y, et al. Hypertension in patients hospitalized with COVID-19 in Wuhan, China: a single-center retrospective observational study. MedRxiv, 2020, 4: 20054825.
10. Wang T, Tang R, Ruan H, et al. Predictors of fatal outcomes among hospitalized COVID-19 patients with pre-existing hypertension in China. Clin Respir J, 2021, 15(8): 915-924.
11. Wang W, Zhao X, Wei W, et al. Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs) may be safe for COVID-19 patients. BMC Infect Dis, 2021, 21(1): 114.
12. Hu J, Zhang X, Zhang X, et al. COVID-19 is more severe in patients with hypertension; ACEI/ARB treatment does not influence clinical severity and outcome. J Infect, 2020, 81(6): 979-997.
13. Gao C, Cai Y, Zhang K, et al. Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study. Eur Heart J, 2020, 41(22): 2058-2066.
14. 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): 825-830.
15. Li X, Xu S, Yu M, et al. Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan. J Allergy Clin Immunol, 2020, 146(1): 110-118.
16. Liu Y, Huang F, Xu J, et al. Anti-hypertensive angiotensinⅡ receptor blockers associated to mitigation of disease severity in elderly COVID-19 patients. MedRxiv, 2020, 3: 20039586.
17. 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): 757-760.
18. Yang G, Tan Z, Zhou L, et al. Effects of angiotensinⅡ receptor blockers and ace (angiotensin-converting enzyme) inhibitors on virus infection, inflammatory status, and clinical outcomes in patients with COVID-19 and hypertension: a single-center retrospective study. Hypertension, 2020, 76(1): 51-58.
19. Huang L, Chen Z, Ni L, et al. Impact of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on the inflammatory response and viral clearance in COVID-19 patients. Front Cardiovasc Med, 2021, 8: 710946.
20. Pan W, Zhang J, Wang M, et al. Clinical features of COVID-19 in patients with essential hypertension and the impacts of renin-angiotensin-aldosterone system inhibitors on the prognosis of COVID-19 patients. Hypertension, 2020, 76(3): 732-741.
21. Meng X, Liu Y, Wei C, et al. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers improved the outcome of patients with severe COVID-19 and hypertension. Sci China Life Sci, 2021, 64(5): 836-839.
22. Wang HY, Peng S, Ye Z, et al. Renin-angiotensin system inhibitor is associated with the reduced risk of all-cause mortality in COVID-19 among patients with/without hypertension. Front Med, 2021: 1-9.
23. Zhang P, Zhu L, Cai J, et al. Association of inpatient use of angiotensin-converting enzyme inhibitors and angiotensinⅡ receptor blockers with mortality among patients with hypertension hospitalized with COVID-19. Circ Res, 2020, 126(12): 1671-1681.
24. 廖玉华, 程翔, 曾秋棠, 等. 湖北省新型冠状病毒肺炎疫情下心血管病治疗与管理专家建议. 临床心血管病杂志, 2020, 36(3): 201-203.
25. Bozkurt B, Kovacs R, Harrington B. Joint HFSA/ACC/AHA statement addresses concerns re: using RAAS antagonists in COVID-19. J Card Fail, 2020, 26(5): 370.
26. Wu C, Chen X, Cai Y, 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, 2020, 180(7): 934-943.
27. Kreutz R, Algharably EAE, Azizi M, et al. Hypertension, the renin-angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19. Cardiovasc Res, 2020, 116(10): 1688-1699.
28. Watkins J. Preventing a COVID-19 pandemic. BMJ, 2020, 368: m810.
29. Ferrario CM, Jessup J, Gallagher PE, et al. Effects of renin-angiotensin system blockade on renal angiotensin-(1-7) forming enzymes and receptors. Kidney Int, 2005, 68(5): 2189-2196.
30. Hamming I, van Goor H, Turner AJ, et al. Differential regulation of renal angiotensin-converting enzyme (ACE) and ACE2 during ACE inhibition and dietary sodium restriction in healthy rats. Exp Physiol, 2008, 93(5): 631-638.
31. Furuhashi M, Moniwa N, Mita T, 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.
32. Mariana CP, Ramona PA, Ioana BC, et al. Urinary angiotensin converting enzyme 2 is strongly related to urinary nephrin in type 2 diabetes patients. Int Urol Nephrol, 2016, 48(9): 1491-1497.
33. Vuille-dit-Bille RN, Camargo SM, Emmenegger L, et al. Human intestine luminal ACE2 and amino acid transporter expression increased by ACE-inhibitors. Amino Acids, 2015, 47(4): 693-705.
34. Imai Y, Kuba K, Rao S, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature, 2005, 436(7047): 112-116.
35. Ferrario CM, Strawn WB. Role of the renin-angiotensin-aldosterone system and proinflammatory mediators in cardiovascular disease. Am J Cardiol, 2006, 98(1): 121-128.
36. Huang F, Guo J, Zou Z, et al. Angiotensin II plasma levels are linked to disease severity and predict fatal outcomes in H7N9-infected patients. Nat Commun, 2014, 5: 3595.
37. Pinter M, Kwanten WJ, Jain RK. Renin-angiotensin system inhibitors to mitigate cancer treatment-related adverse events. Clin Cancer Res, 2018, 24(16): 3803-3812.
38. Hsu WT, Galm BP, Schrank G, et al. Effect of renin-angiotensin-aldosterone system inhibitors on short-term mortality after sepsis: a population-based cohort study. Hypertension, 2020, 75(2): 483-491.
39. Henry C, Zaizafoun M, Stock E, et al. Impact of angiotensin-converting enzyme inhibitors and statins on viral pneumonia. Proc (Bayl Univ Med Cent), 2018, 31(4): 419-423.
40. Vaduganathan M, Vardeny O, Michel T, et al. Renin-angiotensin-aldosterone system inhibitors in patients with COVID-19. N Engl J Med, 2020, 382(17): 1653-1659.
41. Kai H, Kai M. Interactions of coronaviruses with ACE2, angiotensinⅡ, and RAS inhibitors-lessons from available evidence and insights into COVID-19. Hypertens Res, 2020, 43(7): 648-654.
42. Gilstrap LG, Fonarow GC, Desai AS, 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(2): e004675.

Chinese Journal of Evidence-Based Medicine

Impact of ACEI/ARB on clinical outcomes in Chinese patients with COVID-19: a meta-analysis

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