• Imad M Tleyjeh, Aref A Bin Abdulhak, Haytham Tlayjeh, Mouaz H Al-Mallah, M Rizwan Sohail, Leslie C Hassett, Jolanta M Siller-Matula, and Tarek Kashour.
• Department of Medical Specialties, Infectious Diseases Section, King Fahad Medical City, Riyadh, Saudi Arabia; Division of Infectious Diseases, Mayo Clinic College of Medicine and Science, Rochester, MN; Division of Epidemiology, Mayo Clinic College of Medicine and Science, Rochester, MN; College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; Swedish Heart and Vascular Institute, Swedish Medical Center, Seattle, WA; Department of Intensive Care, King Abdulaziz Medical City, King Saud bin Abdulaziz for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; Houston Methodist DeBakey Heart and Vascular Center, Houston, TX; Department of Cardiovascular Diseases, Mayo Clinic College of Medicine and Science, Rochester, MN; Mayo Clinic Libraries, Mayo Clinic, Rochester, MN; Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria; Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology, Medical University of Warsaw, Poland; and Department of Cardiac Sciences, King Fahad Cardiac Center, King Saud University Medical City, Riyadh, Saudi Arabia.
• Am J Ther. 2020 Dec 28; Publish Ahead of Print.

BackgroundSARS-CoV-2 infects its target cells via angiotensin converting enzyme 2 receptor, a membrane-bound protein found on the surface of many human cells. Treatment with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptors blockers (ARB) has been shown to increase angiotensin converting enzyme 2 expression by up to 5-fold.Areas Of UncertaintyThese findings coupled with observations of the high prevalence and mortality among SARS-CoV-2-infected patients with underlying cardiovascular disease have led to a speculation that ACEIs/ARBs may predispose to higher risk of being infected with SARS-CoV-2. Therefore, we systematically reviewed the literature and performed a meta-analysis of the association between prior use of ACEIs and ARBs and the risk of SARS-CoV-2 infection or hospitalization due to COVID-19 disease.Data SourcesWe searched Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus, and Medrxiv.org preprint server until June 18, 2020.Therapeutic AdvancesTen studies (6 cohorts and 4 case control) that enrolled a total of 23,892 patients and 853,369 controls were eligible for inclusion in our meta-analysis. One study was excluded from the analysis because of high risk of bias. Prior use of ACEIs was not associated with an increased risk of acquiring SARS-CoV-2 or hospitalization due to COVID-19 disease, odds ratio 0.98, 95% confidence interval (0.91-1.05), I2 = 15%. Similarly, prior use of ARBs was not associated with an increased risk of acquiring SARS-CoV-2, odds ratio 1.04, 95% confidence interval (0.98-1.10), I2 = 0%.ConclusionCumulative evidence suggests that prior use of ACEIs or ARBs is not associated with a higher risk of COVID-19 or hospitalization due to COVID-19 disease. Our results provide a reassurance to the public not to discontinue prescribed ACEIs/ARBs because of fear of COVID-19.Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

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