Mortality and Disease Severity Among COVID-19 Patients Receiving Renin-Angiotensin System Inhibitors: A Systematic Revie
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SYSTEMATIC REVIEW
Mortality and Disease Severity Among COVID‑19 Patients Receiving Renin‑Angiotensin System Inhibitors: A Systematic Review and Meta‑analysis Syed Shahzad Hasan1 · Chia Siang Kow2 · Muhammad Abdul Hadi3 · Syed Tabish Razi Zaidi4,5 · Hamid A. Merchant1 Accepted: 29 August 2020 © Springer Nature Switzerland AG 2020
Abstract Introduction The use of renin-angiotensin system (RAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), was alleged to cause a more severe course of novel coronavirus disease 2019 (COVID-19). Methods We systematically reviewed the published studies to assess the association of RAS inhibitors with mortality as well as disease severity in COVID-19 patients. A systematic literature search was performed to retrieve relevant original studies investigating mortality and severity (severe/critical disease) in COVID-19 patients with and without exposure to RAS inhibitors. Results A total of 59 original studies were included for qualitative synthesis. Twenty-four studies that reported adjusted effect sizes (24 studies reported mortality outcomes and 16 studies reported disease severity outcomes), conducted in RAS inhibitor–exposed and unexposed groups, were pooled in random-effects models to estimate overall risk. Quality assessment of studies revealed that most of the studies included were of fair quality. The use of an ACEI/ARB in COVID-19 patients was significantly associated with lower odds (odds ratio [OR] = 0.73, 95% confidence interval [CI] 0.56–0.95; n = 18,749) or hazard (hazard ratio [HR] = 0.75, 95% CI 0.60–0.95; n = 26,598) of mortality compared with non-use of ACEI/ARB. However, the use of an ACEI/ARB was non-significantly associated with lower odds (OR = 0.91, 95% CI 0.75–1.10; n = 7446) or hazard (HR = 0.73, 95% CI 0.33–1.66; n = 6325) of developing severe/critical disease compared with non-use of an ACEI/ARB. Discussion Since there was no increased risk of harm, the use of RAS inhibitors for hypertension and other established clinical indications can be maintained in COVID-19 patients.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s40256-020-00439-5) contains supplementary material, which is available to authorized users. * Syed Shahzad Hasan [email protected] 1
Department of Pharmacy, University of Huddersfield, Huddersfield HD1 3DH, UK
2
School of Postgraduate Studies, International Medical University, Kuala Lumpur 57000, Malaysia
3
Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
4
School of Healthcare, University of Leeds, Leeds LS2 9JT, UK
5
Leeds Teaching Hospitals NHS Trust, Leeds LS2 9JT, UK
Key Points The use of renin-angiotensin system (RAS) inhibitors is alleged to cause a more severe course of coronavirus disease 2019 (COVID-19). We systematically reviewed the published studies to assess the association of RAS inhibitors with mortality as well as disease severity in COVID-19 pati
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