Cited by 35COVID-19 Clinical Research StudiesSARS-CoV-2 and COVID-19 ResearchRenin-Angiotensin System Studies

Angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers and the risk of COVID-19 infection or severe disease: Systematic review and meta-analysis

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Caldeira, Daniel, Alves, Mariana, Gouveia e Melo, Ryan, Silvério António, Pedro, Cunha, Nélson, Nunes-Ferreira, Afonso, Prada, Luisa, Costa, João +1 more·2020·IJC Heart & Vasculature

Abstract

Animal studies suggested that angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-receptor blockers (ARB) facilitate the inoculation of potentially leading to a higher risk of infection and/or disease severity. We aimed to systematically evaluate the risk of COVID-19 infection and the risk of severe COVID-19 disease associated with previous exposure to (ACEi) and/or ARB). MEDLINE, CENTRAL, PsycINFO, Web of Science Core Collection were searched in June 2020 for controlled studies. Eligible studies were included and random-effects meta-analyses were performed. The estimates were expressed as odds ratios (OR) and 95% confidence intervals (95%CI). Heterogeneity was assessed with I2 test. The confidence in the pooled evidence was appraised using the GRADE framework. Twenty-seven studies were included in the review. ACEi/ARB exposure did not increase the risk of having a positive test for COVID-19 infection (OR 0.99, 95%CI 0.89–1.11; I2 = 36%; 5 studies, GRADE confidence moderate). The exposure to ACEi/ARB did not increase the risk of all-cause mortality among patients with COVID-19 (OR 0.91, 95%CI 0.74–1.11; I2 = 20%; 17 studies; GRADE confidence low) nor severe/critical COVID-19 disease (OR 0.90, 95%CI 0.74–1.11; I2 = 55%; 17 studies; GRADE confidence very low). Exploratory analyses in studies enrolling hypertensive patients showed a association of ACEi/ARB with a significant decrease of mortality risk. ACEi/ARB exposure does not seem to increase the risk of having the SARS-CoV-2 infection or developing severe stages of the disease including mortality. The potential benefits observed in mortality of hypertensive patients reassure safety, but robust studies are required to increase the confidence in the results.

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  • AngII-AT1R axis inhibitors may be beneficial for COVID-19 patients to decrease serum IL-6 levels.

    “Consistent with animal models, it was reported that AngII–AT1R axis inhibitors may be beneficial for COVID-19 patients (360–363) to decrease serum IL-6 levels (360).”

    From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [363]

    The Results > Sub-analyses and Discussion report an exploratory association between ACE inhibitor or ARB use and lower mortality in COVID-19 patients with hypertension, while cautioning that the evidence cannot establish a definite benefit. The paper does not report that these drugs decrease serum IL-6 levels; a search for serum IL-6 found no supporting passage. (LLM, conf=0.86)

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Research works printed but not linked: 7

  1. [1]WHO. Coronavirus disease 2019 (COVID-19): situation report, vol. 129, 2020.
  2. [4]Stroup D.F. Berlin J.A. Morton S.C. Olkin I. Williamson G.D. Rennie D. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group JAMA 283 2000 2008 2012 10789670
  3. [12]J.A.C.E.M. Sterne, D. Moher, I. Boutron (Eds.), Chapter 10: Addressing reporting biases, Cochrane Handbook for Systematic Reviews of Interventions version 520 (updated June 2017), Cochrane, 2017. Available from: www.training.cochrane.org/handbook.
  4. [13]H.J.O.A. Schünemann, J.P.T. Higgins, G.E. Vist, P. Glasziou, E. Akl, G.H. Guyatt, on behalf of the Cochrane GRADEing Methods Group and the Cochrane Statistical Methods Group. Chapter 11: Completing ‘Summary of findings’ tables and grading the confidence in or quality of the evidence, in: J.P.T.C.R. Higgins, J. Chandler, M.S. Cumpston (Eds.), Cochrane Handbook for Systematic Reviews of Interventions version 520 (updated June 2017), Cochrane; 2017. Available from: www.training.cochrane.org/handbook.
  5. [21]G. Yang, Z. Tan, L. Zhou, M. Yang, L. Peng, J. Liu, et al., Effects Of ARBs And ACEIs On Virus Infection, Inflammatory Status And Clinical Outcomes In COVID-19 Patients With Hypertension: A Single Center Retrospective Study, Hypertension (Dallas, Tex: 1979). 2020. 32348166
  6. [28]R. Gnavi, M. Demaria, R. Picariello, M. Dalmasso, F. Ricceri, G. Costa, Therapy with agents acting on the renin-angiotensin system and risk of SARS-CoV-2 infection, Clinical infectious diseases: an official publication of the Infectious Diseases Society of America, 2020. PMC7543878 32442294
  7. [34]Bean D.M. Kraljevic Z. Searle T. Bendayan R. Kevin O.G. Pickles A. ACE-inhibitors and Angiotensin-2 Receptor Blockers are not associated with severe SARS-COVID19 infection in a multi-site UK acute Hospital Trust Eur. J. Heart Fail. 2020 PMC7301045 32485082

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Authors
Caldeira, D., Alves, M., Gouveia e Melo, R., Silvério António, P., Cunha, N., Nunes-Ferreira, A., Prada, L., Costa, J., & Pinto, F. J.
Affiliations
  • University of Lisbon (PT)
  • Centro Cardiovascular da Universidade de Lisboa (PT)
Corresponding author
Caldeira, Daniel
Venue
IJC Heart & Vasculature
Publisher
Elsevier BV
Published
2020-12
Volume
31
Pages
100627
ISSN
2352-9067 (ISSN-L)
OpenAlex
W3081277611
Cited by
35
References
49
Citations by year
2025: 1 · 2024: 2 · 2023: 3 · 2022: 12 · 2021: 14 · 2020: 3
FWCI
0.38
Type
journal article
Language
en
Open access
Locations
  • IJC Heart & Vasculature (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
Keywords
ACE inhibitors, angiotensin receptor blockers, COVID-19 pandemic, COVID-19 severity, all-cause mortality, hypertension, drug safety, renin-angiotensin system

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