All-cause and in-hospital mortality after aspirin use in patients hospitalized with COVID-19: a systematic review and meta-analysis

  1. Nischit Baral
  2. Joshua D Mitchell
  3. Pramod K Savarapu
  4. Maxwell Akanbi
  5. Bandana Acharya
  6. Soumya Kambalapalli
  7. Amith Seri
  8. Krishna P Bashyal
  9. Arvind Kunadi
  10. Niranjan Ojha
  11. Annabelle Santos Volgman
  12. Tripti Gupta
  13. Timir K Paul

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Abstract

Background

With the results of the largest randomized controlled trial (RECOVERY) and the most extensive retrospective cohort study on coronavirus disease 2019 (COVID-19) recently published, we performed a meta-analysis on the association of aspirin with mortality of COVID-19. We aimed to investigate the role of aspirin in COVID-19 hospitalizations.

Materials and Methods

We searched PubMed, EMBASE and Cochrane databases for studies from 1 January 2020 until 20 July 2022, that compared aspirin versus non-aspirin use in hospitalized COVID-19 patients. We excluded case reports, review articles and studies on non-hospitalized COVID-19 infections. We used the inverse variance method and random effects model to pool the individual studies.

Results

Ten observational studies and one randomized controlled trial met the criteria for inclusion. There were 136 695 total patients, of which 27 168 were in the aspirin group and 109 527 were in the non-aspirin group. Aspirin use was associated with a 14% decrease in all-cause mortality compared with non-aspirin use in patients hospitalized with COVID-19 [relative risk (RR) 0.86, confidence interval (95% CI) 0.76–0.97; P = 0.002; I2 =64%]. Among subgroups of studies reporting in-hospital mortality in COVID-19 hospitalizations, aspirin use was associated with a 16% decrease in in-hospital mortality compared with non-aspirin use (RR 0.84, 95% CI 0.71–0.99; P = 0.007; I2 =64%).

Conclusion

Our study shows that aspirin decreases in-hospital mortality in patients hospitalized with COVID-19. Further studies are needed to assess which COVID-19 patient populations benefit most, such as patients on aspirin for primary versus secondary prevention of atherosclerotic disease. In addition, significant bleeding also needs to be considered when assessing the risk–benefit of aspirin use.

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  1. Version published to 10.1093/biomethods/bpac027
  2. ScreenIT

    SciScore for 10.1101/2021.07.08.21260236: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    We searched PubMed, Google scholar and Clinical trials.gov from inception until May 6, 2021 to identify studies that investigated the effect of low dose aspirin on mortality among adults hospitalized for COVID-19, with no language restrictions.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Google scholar
    suggested: (Google Scholar, RRID:SCR_008878)
    2.4 Study Design: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for reporting systematic reviews as recommended by the Cochrane Collaboration was followed in this systematic review3.
    Cochrane Collaboration
    suggested: None
    2.5 Data collection process: Search results were saved in EndNote version X9 (Developer: Clarivate analysis) files and transferred into Covidence software4.
    EndNote
    suggested: (EndNote, RRID:SCR_014001)

    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 many other limitations. Firstly, all the studies included in the meta-analysis are observational as no RCTs are available comparing aspirin to no aspirin at this time. There is an increased risk of publication bias and other reporting biases such as selective outcome reporting. Nonetheless, to reduce confounding and selection bias, most of the studies in the analysis used propensity scores. The third limitation is that most studies are single-center studies conducted in China and the United States. One of the studies included patients from VA, who are disproportionately older, and male compared to the general population. It can affect the generalizability of the study to other ethnic groups. Fourth, most of the studies did not mention the dosing of aspirin. The heterogeneity of the studies is also higher with I2 of 47% and 39% respectively in overall mortality and in hospital mortality. We did not perform meta regression to adjust for this heterogeneity.

    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.

    Results from scite Reference Check: We found no unreliable references.

    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 10.1101/2021.07.08.21260236v1 on medRxiv