Comparison of renin–angiotensin–aldosterone system inhibitors with other antihypertensives in association with coronavirus disease-19 clinical outcomes

  1. Yihienew M. Bezabih
  2. Alemayehu Bezabih
  3. Endalkachew Alamneh
  4. Gregory M. Peterson
  5. Woldesellassie Bezabhe

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Abstract

Background

Reports on the effects of renin–angiotensin–aldosterone system (RAAS) inhibitors on the clinical outcomes of coronavirus disease-19 (COVID-19) have been conflicting. We performed this meta-analysis to find conclusive evidence.

Methods

We searched published articles through PubMed, EMBASE and medRxiv from 5 January 2020 to 3 August 2020. Studies that reported clinical outcomes of patients with COVID-19, stratified by the class of antihypertensives, were included. Random and fixed-effects models were used to estimate pooled odds ratio (OR).

Results

A total 36 studies involving 30,795 patients with COVID-19 were included. The overall risk of poor patient outcomes (severe COVID-19 or death) was lower in patients taking RAAS inhibitors (OR = 0.79, 95% CI: [0.67, 0.95]) compared with those receiving non-RAAS inhibitor antihypertensives. However, further sub-meta-analysis showed that specific RAAS inhibitors did not show a reduction of poor COVID-19 outcomes when compared with any class of antihypertensive except beta-blockers (BBs). For example, compared to calcium channel blockers (CCBs), neither angiotensin-I-converting enzyme inhibitors (ACEIs) (OR = 0.91, 95% CI: [0.67, 1.23]) nor angiotensin-II receptor blockers (ARBs) (OR = 0.90, 95% CI: [0.62, 1.33]) showed a reduction of poor COVID-19 outcomes. When compared with BBs, however, both ACEIs (OR = 0.85, 95% CI: [0.73, 0.99) and ARBs (OR = 0.72, 95% CI: [0.55, 0.94]) showed an apparent decrease in poor COVID-19 outcomes.

Conclusions

RAAS inhibitors did not increase the risk of mortality or severity of COVID-19. Differences in COVID-19 clinical outcomes between different class of antihypertensive drugs were likely due to the underlying comorbidities for which the antihypertensive drugs were prescribed, although adverse effects of drugs such as BBs could not be excluded.

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  1. Version published to 10.1186/s12879-021-06088-6
  2. ScreenIT

    SciScore for 10.1101/2020.05.21.20108993: (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
    We found 53 and 64 articles indexed in PubMed and EMBASE, respectively.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    EMBASE
    suggested: (EMBASE, RRID:SCR_001650)

    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:
    This meta-analysis has several limitations. First, we included a small number of studies that may affect the power of our conclusions. Second, even though all of the included papers were of good quality, propensity matching to address common confounders was performed in only two studies. In addition, there could also be a possibility of publication bias as all odds ratios were less than one (Figure 1), giving an asymmetry in the funnel plot. The other intrinsic problem of comparing one drug therapy to the other is that the indication of a certain antihypertensive usually depends on the presence of another coexisting comorbidity. For example, a comparison of RAAS inhibitors with non-RAAS inhibitors such as BBs might give a false sense of good outcome with RAAS blockers. This is because BBs might be commonly indicated as a rate controller for arrythmias that directly affect the prognosis. However, ACEIs and ARBs have fairly similar indications and our comparison of the risk between these two drugs should be more reliable. In conclusion, the risk of severe COVID-19 or death was less likely in patients receiving RAAS inhibitors compared to those taking non-RAAS inhibitor antihypertensive agents. ACEIs could potentially decrease the severity and mortality of COVID-19.

    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 10.1101/2020.05.21.20108993 on medRxiv