Association Between ACEIs or ARBs Use and Clinical Outcomes in COVID-19 Patients: A Systematic Review and Meta-analysis

  1. Carlos Diaz-Arocutipa
  2. Jose Saucedo-Chinchay
  3. Adrian V. Hernandez

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Abstract

Importance

There is a controversy regarding whether or not to continue angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with coronavirus disease 2019 (COVID-19).

Objective

To evaluate the association between ACEIs or ARBs use and clinical outcomes in COVID-19 patients.

Data Sources

Systematic search of the PubMed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials from database inception to May 31, 2020. We also searched the preprint servers medRxiv and SSNR for additional studies.

Study Selection

Observational studies and randomized controlled trials reporting the effect of ACEIs or ARBs use on clinical outcomes of adult patients with COVID-19.

Data Extraction and Synthesis

Risk of bias of observational studies were evaluated using the Newcastle-Ottawa Scale. Meta-analyses were performed using a random-effects models and effects expressed as Odds ratios (OR) and mean differences with their 95% confidence interval (95%CI). If available, adjusted effects were pooled.

Main Outcomes and Measures

The primary outcome was all-cause mortality and secondary outcomes were COVID-19 severity, hospital discharge, hospitalization, intensive care unit admission, mechanical ventilation, length of hospital stay, and troponin, creatinine, procalcitonin, C-reactive protein (CRP), interleukin-6 (IL-6), and D-dimer levels.

Results

40 studies (21 cross-sectional, two case-control, and 17 cohorts) involving 50615 patients were included. ACEIs or ARBs use was not associated with all-cause mortality overall (OR 1.11, 95%CI 0.77-1.60, p=0.56), in subgroups by study design and using adjusted effects. ACEI or ARB use was independently associated with lower COVID-19 severity (aOR 0.56, 95%CI 0.37-0.87, p<0.01). No significant associations were found between ACEIs or ARBs use and hospital discharge, hospitalization, mechanical ventilation, length of hospital stay, and biomarkers.

Conclusions and Relevance

ACEIs or ARBs use was not associated with higher all-cause mortality in COVID-19. However, ACEI or ARB use was independently associated with lower COVID-19 severity. Our results support the current international guidelines to continue the use of ACEIs and ARBs in COVID-19 patients with hypertension.

Key points

Question

What is the association between angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) use and clinical outcomes in coronavirus disease 2019 (COVID-19) patients?

Findings

In this systematic review and meta-analysis of 40 observational studies, the use of ACEIs or ARBs was not associated with higher all-cause mortality in COVID-19 patients. Additionally, ACEIs or ARBs use was independently associated with lower COVID-19 severity.

Meaning

These results support the current international guidelines to continue the use of ACEIs and ARBs in COVID-19 patients with hypertension.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2020.06.03.20120261: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    RandomizationAdditionally, clinicaltrials.gov registry was searched for finished as well as ongoing randomized controlled trials (RCTs).
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Search strategy: We searched PubMed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Embase
    suggested: (EMBASE, RRID:SCR_001650)
    Cochrane Central Register of Controlled Trials
    suggested: (Cochrane Central Register of Controlled Trials, RRID:SCR_006576)

    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 study has some limitations. First, given most of the studies did not use adjusted effects, there is an increased risk of bias in their pooled effect measures. Thus, these results should be considered with caution. However, we also reported meta-analyses of adjusted estimates of a few available studies. Second, the majority of the included studies were of cross-sectional design, thus causality cannot be concluded due to the methodological limitations of this design. Third, heterogeneity was high in most of the evaluated outcomes. Possible reasons for heterogeneity include sample size, differences in outcome definitions, heterogeneous population, among others. Fourth, given that discontinuation of ACEIs or ARBs during hospitalization was not reported consistently across studies, this could influence the significance of pooled estimates. Finally, we could not adequately evaluate the effects of ACEIs and ARBs by separate, since were mainly reported as aggregate due to scarcity of studies.

    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.

  2. Version published to 10.1101/2020.06.03.20120261v1 on medRxiv