Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2021 Sep 7;10(1):243.
doi: 10.1186/s13643-021-01802-6.

Meta-analysis of the association between angiotensin pathway inhibitors and COVID-19 severity and mortality

Malindu E Fernando  1   2 , Aaron Drovandi  1 , Jonathan Golledge  3   4   5
Affiliations
Meta-Analysis

Meta-analysis of the association between angiotensin pathway inhibitors and COVID-19 severity and mortality

Malindu E Fernando et al. Syst Rev. .

Abstract

Background: Conflicting findings and the analysis of unpublished and retracted data have led to controversy on the safety of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in people with COVID-19 infection. This meta-analysis examined the association of prescription of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) with the outcome from COVID-19.

Methods: A systematic search was conducted to find published studies that reported the outcome of COVID-19 in relation to prescription of ACEI or ARB. Two authors (MF and AD) independently screened and extracted data and assessed study quality and strength of association using standardised tools. The endpoints for the meta-analyses were severe or critical disease outcome and mortality based on standardised criteria.

Results: Twenty-six studies including 8389 people prescribed ACEI or ARB and 20,989 people not prescribed these medications were included. The quality of studies varied, and the overall strength of association was poor with a high risk of confounding bias. Patients prescribed ACEI or ARB had a greater prevalence of risk factors. Meta-analysis found an association between prescription of ACEI or ARB with severe or critical disease outcome (risk ratio, RR, 1.23, 95% confidence interval, CI, 1.06 to 1.42, p = 0.006, I2 = 88%) but this association was lost in sensitivity analyses. There was no association between ACEI or ARB prescription and mortality (RR 1.18, 95% CI 0.92 to 1.50, p = 0.19, I2 = 82%).

Conclusions: This meta-analysis suggests that people prescribed ACEI or ARB more commonly had severe or critical disease outcome, but not mortality, in published cohorts of patients diagnosed with COVID-19. This finding is most likely due to a greater prevalence of risk factors in these patients rather than due to exposure to angiotensin pathway inhibitors.

Keywords: 2019 novel coronavirus disease; Angiotensin receptor blockers; Angiotensin-converting enzyme inhibitors; COVID-19.

PubMed Disclaimer

Conflict of interest statement

None of the authors have any relevant conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
PRISMA flow diagram detailing the search results on the 19th June 2020
Fig. 2
Fig. 2
Forest plot of COVID-19 severity and association with prescription of ACEI/ARB
Fig. 3
Fig. 3
Forest plot of COVID-19 mortality and association with prescription of ACEI/ARB
Fig. 4
Fig. 4
Forest plots of COVID-19 mortality and association with prescription of ACEI/ARB in people with a previous history of hypertension
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Guo YR, Cao QD, Hong ZS, Tan YY, Chen SD, Jin HJ, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Mil Med Res. 2020;7(1):1–10. - PMC - PubMed
    1. Igase M, Strawn WB, Gallagher PE, Geary RL, Ferrario CM. Angiotensin II AT1 receptors regulate ACE2 and angiotensin-(1-7) expression in the aorta of spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol. 2005;289(3):H1013–H1019. doi: 10.1152/ajpheart.00068.2005. - DOI - PubMed
    1. Brojakowska A, Narula J, Shimony R, Bander J. Clinical Implications of SARS-CoV-2 interaction with renin angiotensin system: JACC review topic of the week. J Am Coll Cardiol. 2020;75(24):3085–3095. doi: 10.1016/j.jacc.2020.04.028. - DOI - PMC - PubMed
    1. Wang B, Li R, Lu Z, Huang Y. Does comorbidity increase the risk of patients with COVID-19: evidence from meta-analysis. Aging. 2020;12(7):6049–6057. doi: 10.18632/aging.103000. - DOI - PMC - PubMed
    1. Lippi G, Wong J, Henry BM. Hypertension and its severity or mortality in coronavirus disease 2019 (COVID-19): a pooled analysis. Pol Arch Intern Med. 2020;130(4):304–309. doi: 10.20452/pamw.15272. - DOI - PubMed

Publication types

Substances