Renin–angiotensin–aldosterone system inhibitors and the risk of mortality in patients with hypertension hospitalised for COVID-19: systematic review and meta-analysis

  1. Anna E Ssentongo
  2. Paddy Ssentongo
  3. Emily S Heilbrunn
  4. Alain Lekoubou
  5. Ping Du
  6. Duanping Liao
  7. John S Oh
  8. Vernon M Chinchilli

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Abstract

The association between the use of renin–angiotensin–aldosterone (RAAS) inhibitors and the risk of mortality from COVID-19 is unclear. We aimed to estimate the association of RAAS inhibitors, including ACE inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) with COVID-19 mortality risk in patients with hypertension.

Methods

PubMed (MEDLINE) SCOPUS, OVID, Cochrane Library databases and medrxiv.org were searched from 1 January 2020 to 1 September 2020. Studies reporting the association of RAAS inhibitors (ACEi or ARBs) and mortality in patients with hypertension, hospitalised for COVID-19 were extracted. Two reviewers independently extracted appropriate data of interest and assessed the risk of bias. All analyses were performed using random-effects models on log-transformed risk ratio (RR) estimates, and heterogeneity was quantified.

Results

Fourteen studies were included in the systematic review (n=73,073 patients with COVID-19; mean age 61 years; 53% male). Overall, the between-study heterogeneity was high (I 2 =80%, p<0.01). Patients with hypertension with prior use of RAAS inhibitors were 35% less likely to die from COVID-19 compared with patients with hypertension not taking RAAS inhibitors (pooled RR 0.65, 95% CI 0.45 to 0.94). The quality of evidence by Grading of Recommendations, Assessment, Development and Evaluations was graded as ‘moderate’ quality.

Conclusions

In this meta-analysis, with prior use of RAAS inhibitors was associated with lower risk mortality from COVID-19 in patients with hypertension. Our findings suggest a potential protective effect of RAAS-inhibitors in COVID-19 patients with hypertension.

PROSPERO registration number

The present study has been registered with PROSPERO (registration ID: CRD 42020187963).

Article activity feed

  1. Version published to 10.1136/openhrt-2020-001353
  2. ScreenIT

    SciScore for 10.1101/2020.05.21.20107003: (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 explored PubMed (MEDLINE) Scopus, the OVID databases, SCOPUS, Cochrane Library databases and medrxiv.org, using search criteria provided in the supplemental material (Supplemental Text 1).
    MEDLINE
    suggested: (MEDLINE, RRID:SCR_002185)
    Cochrane Library
    suggested: (Cochrane Library, RRID:SCR_013000)
    The following Medical Subject Heading (MeSH) and key words were used for the literature search of PubMed and other databases: ““receptors, angiotensin” OR “angiotensin” OR “angiotensin receptors” OR “angiotensin converting enzyme inhibitors” “Renin Angiotensin Aldosterone System” OR “Angiotensin Receptor Blocker” OR “Ace Inhibitor” OR “Angiotensin Converting Enzyme Inhibitor” AND “SARS-CoV-2” OR “COVID-19” OR “Coronavirus”.
    MeSH
    suggested: (MeSH, RRID:SCR_004750)
    PubMed
    suggested: (PubMed, RRID:SCR_004846)

    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:
    Strengths and Limitations: Limitations of our study include possible selection bias in the published literature as a result of the strict COVID-19 testing algorithm employed in the early stages of the pandemic. This may have resulted in missed COVID-19 cases or deaths. Nevertheless, this is the largest quantitative synthesis of evidence on the association between RAAS-inhibitor exposure and COVID-19 mortality. The regions with the highest burden of COVID-19, including Asia, Europe, and North America, were represented thus increasing the external validity of our findings. The sample size included in this study was also quite large, allowing us to thoroughly cover a large population.

    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.
    • Thank you for including a protocol registration statement.

    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 10.1101/2020.05.21.20107003v2 on medRxiv
  4. Version published to 10.1101/2020.05.21.20107003v1 on medRxiv