AUTHOR=Dai Xiao-Ce , An Zhuo-Yu , Wang Zi-Yang , Wang Zi-Zhen , Wang Yi-Ren 

TITLE=Associations Between the Use of Renin–Angiotensin System Inhibitors and the Risks of Severe COVID-19 and Mortality in COVID-19 Patients With Hypertension: A Meta-Analysis of Observational Studies

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.609857

DOI=10.3389/fcvm.2021.609857

ISSN=2297-055X

ABSTRACT=<p>Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) share a target receptor with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The use of ACEIs/ARBs may cause angiotensin-converting enzyme 2 receptor upregulation, facilitating the entry of SARS-CoV-2 into host cells. There is concern that the use of ACEIs/ARBs could increase the risks of severe COVID-19 and mortality. The impact of discontinuing these drugs in patients with COVID-19 remains uncertain. We aimed to assess the association between the use of ACEIs/ARBs and the risks of mortality and severe disease in patients with COVID-19. A systematic search was performed in PubMed, EMBASE, Cochrane Library, and <ext-link ext-link-type="uri" xlink:href="http://MedRxiv.org" xmlns:xlink="http://www.w3.org/1999/xlink">MedRxiv.org</ext-link> from December 1, 2019, to June 20, 2020. We also identified additional citations by manually searching the reference lists of eligible articles. Forty-two observational studies including 63,893 participants were included. We found that the use of ACEIs/ARBs was not significantly associated with a reduction in the relative risk of all-cause mortality [odds ratio (OR) = 0.87, 95% confidence interval (95% CI) = 0.75–1.00; <italic>I</italic><sup>2</sup> = 57%, <italic>p</italic> = 0.05]. We found no significant reduction in the risk of severe disease in the ACEI subgroup (OR = 0.95, 95% CI = 0.88–1.02, <italic>I</italic><sup>2</sup> = 50%, <italic>p</italic> = 0.18), the ARB subgroup (OR = 1.03, 95% CI = 0.94–1.13, <italic>I</italic><sup>2</sup> = 62%, <italic>p</italic> = 0.48), or the ACEI/ARB subgroup (OR = 0.83, 95% CI = 0.65–1.08, <italic>I</italic><sup>2</sup> = 67%, <italic>p</italic> = 0.16). Moreover, seven studies showed no significant difference in the duration of hospitalization between the two groups (mean difference = 0.33, 95% CI = −1.75 to 2.40, <italic>p</italic> = 0.76). In conclusion, the use of ACEIs/ARBs appears to not have a significant effect on mortality, disease severity, or duration of hospitalization in COVID-19 patients. On the basis of the findings of this meta-analysis, there is no support for the cessation of treatment with ACEIs or ARBs in patients with COVID-19.</p>