Cardiovascular drugs and COVID‐19 clinical outcomes: A living systematic review and meta‐analysis

  1. Innocent G. Asiimwe
  2. Sudeep Pushpakom
  3. Richard M. Turner
  4. Ruwanthi Kolamunnage‐Dona
  5. Andrea L. Jorgensen
  6. Munir Pirmohamed

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Abstract

The aim of this study was to continually evaluate the association between cardiovascular drug exposure and COVID‐19 clinical outcomes (susceptibility to infection, disease severity, hospitalization, hospitalization length, and all‐cause mortality) in patients at risk of/with confirmed COVID‐19.

Methods

Eligible publications were identified from more than 500 databases on 1 November 2020. One reviewer extracted data with 20% of the records independently extracted/evaluated by a second reviewer.

Results

Of 52 735 screened records, 429 and 390 studies were included in the qualitative and quantitative syntheses, respectively. The most‐reported drugs were angiotensin‐converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) with ACEI/ARB exposure having borderline association with confirmed COVID‐19 infection (OR 1.14, 95% CI 1.00–1.31). Among COVID‐19 patients, unadjusted estimates showed that ACEI/ARB exposure was associated with hospitalization (OR 1.76, 95% CI 1.34–2.32), disease severity (OR 1.40, 95% CI 1.26–1.55) and all‐cause mortality (OR 1.22, 95% CI 1.12–1.33) but not hospitalization length (mean difference −0.27, 95% CI −1.36–0.82 days). After adjustment, ACEI/ARB exposure was not associated with confirmed COVID‐19 infection (OR 0.92, 95% CI 0.71–1.19), hospitalization (OR 0.93, 95% CI 0.70–1.24), disease severity (OR 1.05, 95% CI 0.81–1.38) or all‐cause mortality (OR 0.84, 95% CI 0.70–1.00). Similarly, subgroup analyses involving only hypertensive patients revealed that ACEI/ARB exposure was not associated with confirmed COVID‐19 infection (OR 0.93, 95% CI 0.79–1.09), hospitalization (OR 0.84, 95% CI 0.58–1.22), hospitalization length (mean difference −0.14, 95% CI −1.65–1.36 days), disease severity (OR 0.92, 95% CI 0.76–1.11) while it decreased the odds of dying (OR 0.76, 95% CI 0.65–0.88). A similar trend was observed for other cardiovascular drugs. However, the validity of these findings is limited by a high level of heterogeneity and serious risk of bias.

Conclusion

Cardiovascular drugs are not associated with poor COVID‐19 outcomes in adjusted analyses. Patients should continue taking these drugs as prescribed.

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  1. Version published to 10.1111/bcp.14927
  2. ScreenIT

    SciScore for 10.1101/2020.10.07.20208918: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Identification of studies: A final search of the University of Liverpool’s DISCOVER platform (which links, through EBSCOhost, to sources from >500 databases including MEDLINE, Google Scholar, Scopus, the Web of Science and Cochrane Central Register of Controlled Trial libraries) was undertaken on 31st July 2020 using medical subject headings and text words related to “cardiovascular drugs” and “COVID-19” (Text S1).
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)
    search (Text S1) was conducted to ensure that the DISCOVER search was retrieving all eligible records.
    DISCOVER
    suggested: (discovering-cse, RRID:SCR_011832)
    Preprint servers (bioRxiv and medRxiv, Text S1), COVID-19 specific databases (such as the COVID-19 Clinical Trials registry and the World Health Organization database of COVID-19 publications), other registries/results databases (such as ClinicalTrials.gov and the International Clinical Trials Registry Platform) and grey literature were also searched to identify further eligible studies.
    bioRxiv
    suggested: (bioRxiv, RRID:SCR_003933)
    Data extraction: Two reviewers (IGA for DISCOVER and SP for MEDLINE) independently screened titles and abstracts of the retrieved bibliographic records according to eligibility.
    MEDLINE
    suggested: (MEDLINE, RRID:SCR_002185)
    Assessment of study quality: To assess the quality of each included study estimate, the revised Cochrane risk-of-bias tool for randomized trials31 and ROBINS-I (
    Cochrane
    suggested: (Cochrane Library, RRID:SCR_013000)
    48 Where necessary, means and standard deviations were combined using formulae available in the Cochrane Handbook.
    Cochrane Handbook
    suggested: None
    Supplementary Methods, Figures and Tables:
    Tables
    suggested: (ObjTables, RRID:SCR_018652)

    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:
    Limitations of this review: For most of the meta-analyses, heterogeneity in effect estimates was high, which is similar to previous observations.10,12-14,17,18,21 Consequently, following GRADE rating,52,53 all estimates with high heterogeneity (I2 >70) were downgraded by one level (high to moderate certainty rating). Additionally, almost all estimates were ranked to be at a serious risk of bias. This differs from previous reviews in which many studies were considered to have low to moderate risk of bias,10-18,20,21 a contradiction we attribute to the risk of bias assessment tools used (whereas we used the ROBINS-I [Risk Of Bias In Non-randomised Studies – of Interventions] tool for non-randomized studies,32 other reviews used the Newcastle Ottawa Scale). Again following GRADE52,53 recommendations, the evidence certainty rating was downgraded by one level for estimates with a serious risk of bias (from high to moderate or from moderate to low). Despite our comprehensive search strategy and to facilitate timely publication, we did not contact study authors for data that was required to enable meta-analysis but not reported in the published paper, and therefore did not include studies that could potentially be eligible. We were also unable to include many studies from some preprint servers such as Authorea.com, Preprints from Lancet, and Preprints.org. We were however cognizant of the fact that this is a living systematic review and any studies that we excluded due to data neede...

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

    IdentifierStatusTitle
    NCT04343001WithdrawnCoronavirus Response - Active Support for Hospitalised Covid…
    NCT04328012RecruitingCOVID MED Trial - Comparison Of Therapeutics for Hospitalize…
    NCT04349410CompletedThe Fleming [FMTVDM] Directed CoVid-19 Treatment Protocol

    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.

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  3. Version published to 10.1101/2020.10.07.20208918v1 on medRxiv