Association between angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers use and the risk of infection and clinical outcome of COVID-19: a comprehensive systematic review and meta-analysis

  1. Guangbo Qu
  2. Liqin Shu
  3. Evelyn J. Song
  4. Dhiran Verghese
  5. John Patrick Uy
  6. Ce Cheng
  7. Qin Zhou
  8. Hongru Yang
  9. Zhichun Guo
  10. Mengshi Chen
  11. Chenyu Sun

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Abstract

Background

The effect of using Angiotensin-converting enzyme inhibitors (ACEIs) and Angiotensin-receptor blockers (ARBs) on the risk of coronavirus disease 2019 (COVID-19) is a topic of recent debate. Although studies have examined the potential association between them, the results remain controversial. This study aims to determine the true effect of ACEI/ARBs use on the risk of infection and clinical outcome of COVID-19.

Methods

Five electronic databases (PubMed, Web of science, Cochrane library, China National Knowledge Infrastructure database, medRxiv preprint server) were retrieved to find eligible studies. Meta-analysis was performed to examine the association between ACEI/ARBs use and the risk of infection and clinical outcome of COVID-19.

Results

22 articles containing 157,328 patients were included. Use of ACEI/ARBs was not associated with increased risk of infection (Adjusted OR: 0.96, 95% CI: 0.91-1.01, I 2 =5.8%) or increased severity (Adjusted OR: 0.90, 95% CI: 0.77-1.05, I 2 =27.6%) of COVID-19. The use of ACEI/ARBs was associated with lower risk of death from COVID-19 (Adjusted OR: 0.66, 95% CI: 0.44-0.99, I 2 =57.9%). Similar results of reduced risk of death were also found for ACEI/ARB use in COVID-19 patients with hypertension (Adjusted OR: 0.36, 95% CI: 0.17-0.77, I 2 =0).

Conclusion

This study provides evidence that ACEI/ARBs use for COVID-19 patients does not lead to harmful outcomes and may even provide a beneficial role and decrease mortality from COVID-19. Clinicians should not discontinue ACEI/ARBs for patients diagnosed with COVID-19 if they are already on these agents.

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  1. Version published to 10.1101/2020.07.02.20144717v2 on medRxiv
  2. ScreenIT

    SciScore for 10.1101/2020.07.02.20144717: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    2.1 Literature search and data source: We searched five electronic databases (PubMed, Web of science, Cochrane library, China National Knowledge Infrastructure database, medRxiv preprint server) to collect relevant studies published until May 20, 2020.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Cochrane library
    suggested: (Cochrane Library, RRID:SCR_013000)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    A few limitations present in our study should be noted. First, all the studies included are observational studies, making it difficult to infer accurate causation. Second, no data was provided regarding the dose and exposure duration of ACEI/ARBs; therefore, we could not determinate whether COVID-19 infection is affected by the dose and duration of ACEI/ARBs exposure. Third, beta blockers can also prevent ACE2 activity [52], therefore, the effect of ACEI/ARB use may be underestimated for patients with CVD who also take beta blockers. Finally, given that some important confounders (such as comorbidities) have not been adjusted for in the included studies, the true association between ACEI/ARB use and the risk of hospitalization could not be well inferred. Conclusion: In conclusion, ACEI/ARB use does not affect the risk and severity of COVID-19 infection and actually leads to a decreased mortality from COVID-19. The effect of ACEI/ARB use on hospitalization needs to be further assessed with adjusting for potential confounders. The potential protective role of ACEI/ARB supports the recommendation that these agents should not be discontinued for COVID-19 patients if they are already on them.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2020.07.02.20144717v1 on medRxiv