A systematic review and meta-analysis to evaluate the clinical outcomes in COVID-19 patients on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers

  1. Abhinav Grover
  2. Mansi Oberoi

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Abstract

Introduction

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) share their target receptor site with the SARS-CoV-2 virus, that may cause ACE2 receptor up-regulation which raised concerns regarding ACEI and ARB use in COVID-19 patients. However, many medical professional societies recommended their continued use given the paucity of clinical evidence, but there is a need for an updated systematic review and meta-analysis of the latest clinical studies.

Methods and results

A search was conducted on PubMed, Google Scholar, EMBASE, and various preprint servers for studies comparing clinical outcomes and mortality in COVID-19 patients on ACEIs and/or ARBs, and a meta-analysis was performed. A total of 16 studies were included for the review and meta-analysis. There were conflicting findings reported in the rates of severity and mortality in several studies. In a pooled analysis of four studies, there was a statistically non-significant association of ACEI/ARB use with lower odds of developing severe disease vs. non-users [odds ratio (OR) = 0.81, 95% confidence interval (CI): 0.41–1.58, I2=50.52, P-value = 0.53). In a pooled analysis of six studies, there was a statistically non-significant association of ACEI/ARB use with lower odds of mortality as compared with non-users (OR = 0.86, 95% CI = 0.53–1.41, I2 = 79.12, P-value = 0.55).

Conclusion

It is concluded that ACEIs and ARBs should be continued in COVID-19 patients, reinforcing the recommendations made by several medical societies. Additionally, the individual patient factors such as ACE2 polymorphisms which might confer higher risk of adverse outcomes need to be evaluated further.

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  1. Version published to 10.1093/ehjcvp/pvaa064
  2. ScreenIT

    SciScore for 10.1101/2020.04.29.20085787: (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
    Literature Search: Literature search was conducted on the PubMed/MEDLINE database using key words, viz.
    PubMed/MEDLINE
    suggested: None
    Additional papers of possible interest were identified by examining references of pertinent review articles and searching Google Scholar and preprint servers like MedRxiv and Biorxiv.
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)
    Biorxiv
    suggested: (bioRxiv, RRID:SCR_003933)

    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:
    Our review has limitations in its rigor due to the scarce existing data and diverse study types available. The rapidly emerging knowledge base of COVID-19 poses the possibility that few studies (particularly unpublished/under peer review) remain un-captured. However, we have tried our best to mitigate this by allowing broadest search terms and by including many databases and repositories. We have also tried to comprehensively review and analyze the existing data. Considering the inconsistent clinical studies and conflicting hypothesis, it is essential to evaluate the clinical outcomes in COVID-19 patients on ACEI/ARB in future large studies, particularly randomized controlled trials and additionally evaluate the association of clinical outcomes with ACE2 polymorphisms. Based on this, there are ongoing trials studying the effect of Losartan (an ARB) in patients with COVID-19 in outpatient and inpatient settings (NCT04311177, NCT04312009) [34,35].

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04311177CompletedLosartan for Patients With COVID-19 Not Requiring Hospitaliz…
    NCT04312009CompletedLosartan for Patients With COVID-19 Requiring Hospitalizatio…

    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

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  3. Version published to 10.1101/2020.04.29.20085787v2 on medRxiv
  4. Version published to 10.1101/2020.04.29.20085787v1 on medRxiv