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Renin-Angiotensin-Aldosterone System Inhibitors and Risks of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Systematic Review and Meta-Analysis.
Hypertension. 2020 11; 76(5):1563-1571.H

Abstract

The viral spike coat protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) engages the human ACE (angiotensin-converting enzyme) 2 cell surface receptor to infect the host cells. Thus, concerns arose regarding theoretically higher risk for coronavirus disease-19 (COVID-19) in patients taking ACE inhibitors/angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]). We systematically assessed case-population and cohort studies from MEDLINE (Ovid), Cochrane Database of Systematic Reviews PubMed, Embase, medRXIV, the World Health Organization database of COVID-19 publications, and ClinicalTrials.gov through June 1, 2020, with planned ongoing surveillance. We rated the certainty of evidence according to Cochrane methods and the Grading of Recommendations Assessment, Development and Evaluation approach. After pooling the adjusted odds ratios from the included studies, no significant increase was noted in the risk of SARS-CoV-2 infection by the use of ACE inhibitors (adjusted odds ratio, 0.95 [95% CI, 0.86-1.05]) or ARBs (adjusted odds ratio, 1.05 [95% CI, 0.97-1.14]). However, the random-effects meta-regression revealed that age may modify the SARS-CoV-2 infection risk in subjects with the use of ARBs (coefficient, -0.006 [95% CI, -0.016 to 0.004]), that is, the use of ARBs, as opposed to ACE inhibitors, specifically augmented the risk of SARS-CoV-2 infection in younger subjects (<60 years old). The use of ACE inhibitors might not increase the susceptibility of SARS-CoV-2 infection, severity of disease, and mortality in case-population and cohort studies. Additionally, we discovered for the first time that the use of ARBs, as opposed to ACE inhibitors, specifically augmented the risk of SARS-CoV-2 infection in younger subjects, without obvious effects on COVID-19 outcomes.

Authors+Show Affiliations

From the Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsin Chu County (C.-K.C.). Department of Internal Medicine (C.-K.C., Y.-S.H., J.-T.W., V.-C.W., T.-S.C.), National Taiwan University Hospital, Taipei. Graduate Institute of Clinical Medicine, College of Medicine (C.-K.C., Y.-S.H.), National Taiwan University Hospital, Taipei.Department of Internal Medicine (C.-K.C., Y.-S.H., J.-T.W., V.-C.W., T.-S.C.), National Taiwan University Hospital, Taipei. Graduate Institute of Clinical Medicine, College of Medicine (C.-K.C., Y.-S.H.), National Taiwan University Hospital, Taipei.Chinru Clinic, Taipei, Taiwan (H.-W.L.).Division of Nephrology, Department of Pediatrics, National Taiwan University Children's Hospital, Taipei (I.-J.T.).Division of Nephrology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Taiwan (C.-Y.S., H.-C.P.).Division of Nephrology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Taiwan (C.-Y.S., H.-C.P.).Glickman Urological and Kidney Institute, and Cleveland Clinic Lerner College of Medicine, OH (J.S.C.).Department of Internal Medicine (C.-K.C., Y.-S.H., J.-T.W., V.-C.W., T.-S.C.), National Taiwan University Hospital, Taipei.Department of Internal Medicine (C.-K.C., Y.-S.H., J.-T.W., V.-C.W., T.-S.C.), National Taiwan University Hospital, Taipei. NSARF (National Taiwan University Hospital Study Group of ARF), TAIPAI, (Taiwan Primary Aldosteronism Investigators), and CAKS (Taiwan Consortium for Acute Kidney Injury and Renal Diseases), Taipei (V.-C.W.).Department of Internal Medicine (C.-K.C., Y.-S.H., J.-T.W., V.-C.W., T.-S.C.), National Taiwan University Hospital, Taipei.No affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Systematic Review

Language

eng

PubMed ID

32869673

Citation

Chan, Chieh-Kai, et al. "Renin-Angiotensin-Aldosterone System Inhibitors and Risks of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: a Systematic Review and Meta-Analysis." Hypertension (Dallas, Tex. : 1979), vol. 76, no. 5, 2020, pp. 1563-1571.
Chan CK, Huang YS, Liao HW, et al. Renin-Angiotensin-Aldosterone System Inhibitors and Risks of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Systematic Review and Meta-Analysis. Hypertension. 2020;76(5):1563-1571.
Chan, C. K., Huang, Y. S., Liao, H. W., Tsai, I. J., Sun, C. Y., Pan, H. C., Chueh, J. S., Wang, J. T., Wu, V. C., & Chu, T. S. (2020). Renin-Angiotensin-Aldosterone System Inhibitors and Risks of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Systematic Review and Meta-Analysis. Hypertension (Dallas, Tex. : 1979), 76(5), 1563-1571. https://doi.org/10.1161/HYPERTENSIONAHA.120.15989
Chan CK, et al. Renin-Angiotensin-Aldosterone System Inhibitors and Risks of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: a Systematic Review and Meta-Analysis. Hypertension. 2020;76(5):1563-1571. PubMed PMID: 32869673.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Renin-Angiotensin-Aldosterone System Inhibitors and Risks of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Systematic Review and Meta-Analysis. AU - Chan,Chieh-Kai, AU - Huang,Yu-Shan, AU - Liao,Hung-Wei, AU - Tsai,I-Jung, AU - Sun,Chiao-Yin, AU - Pan,Heng-Chih, AU - Chueh,Jeff S, AU - Wang,Jann-Tay, AU - Wu,Vin-Cent, AU - Chu,Tzong-Shinn, AU - ,, Y1 - 2020/09/01/ PY - 2020/9/2/pubmed PY - 2020/10/21/medline PY - 2020/9/2/entrez KW - ACE inhibitors KW - angiotensin receptor antagonists KW - angiotensin-converting enzyme2 KW - coronavirus KW - meta-analysis KW - renin-angiotensin-aldosterone system KW - severe acute respiratory syndrome coronavirus 2 SP - 1563 EP - 1571 JF - Hypertension (Dallas, Tex. : 1979) JO - Hypertension VL - 76 IS - 5 N2 - The viral spike coat protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) engages the human ACE (angiotensin-converting enzyme) 2 cell surface receptor to infect the host cells. Thus, concerns arose regarding theoretically higher risk for coronavirus disease-19 (COVID-19) in patients taking ACE inhibitors/angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]). We systematically assessed case-population and cohort studies from MEDLINE (Ovid), Cochrane Database of Systematic Reviews PubMed, Embase, medRXIV, the World Health Organization database of COVID-19 publications, and ClinicalTrials.gov through June 1, 2020, with planned ongoing surveillance. We rated the certainty of evidence according to Cochrane methods and the Grading of Recommendations Assessment, Development and Evaluation approach. After pooling the adjusted odds ratios from the included studies, no significant increase was noted in the risk of SARS-CoV-2 infection by the use of ACE inhibitors (adjusted odds ratio, 0.95 [95% CI, 0.86-1.05]) or ARBs (adjusted odds ratio, 1.05 [95% CI, 0.97-1.14]). However, the random-effects meta-regression revealed that age may modify the SARS-CoV-2 infection risk in subjects with the use of ARBs (coefficient, -0.006 [95% CI, -0.016 to 0.004]), that is, the use of ARBs, as opposed to ACE inhibitors, specifically augmented the risk of SARS-CoV-2 infection in younger subjects (<60 years old). The use of ACE inhibitors might not increase the susceptibility of SARS-CoV-2 infection, severity of disease, and mortality in case-population and cohort studies. Additionally, we discovered for the first time that the use of ARBs, as opposed to ACE inhibitors, specifically augmented the risk of SARS-CoV-2 infection in younger subjects, without obvious effects on COVID-19 outcomes. SN - 1524-4563 UR - https://www.unboundmedicine.com/medline/citation/32869673/Renin_Angiotensin_Aldosterone_System_Inhibitors_and_Risks_of_Severe_Acute_Respiratory_Syndrome_Coronavirus_2_Infection:_A_Systematic_Review_and_Meta_Analysis_ DB - PRIME DP - Unbound Medicine ER -