Intermediate‐dose anticoagulation, aspirin, and in‐hospital mortality in COVID ‐19: A propensity score‐matched analysis

  1. Matthew L. Meizlish
  2. George Goshua
  3. Yiwen Liu
  4. Rebecca Fine
  5. Kejal Amin
  6. Eric Chang
  7. Nicholas DeFilippo
  8. Craig Keating
  9. Yuxin Liu
  10. Michael Mankbadi
  11. Dayna McManus
  12. Stephen Y. Wang
  13. Christina Price
  14. Robert D. Bona
  15. Cassius Iyad Ochoa Chaar
  16. Hyung J. Chun
  17. Alexander B. Pine
  18. Henry M. Rinder
  19. Jonathan M. Siner
  20. Donna S. Neuberg
  21. Kent A. Owusu
  22. Alfred Ian Lee

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Abstract

Thrombotic complications occur at high rates in hospitalized patients with COVID‐19, yet the impact of intensive antithrombotic therapy on mortality is uncertain. We examined in‐hospital mortality with intermediate‐ compared to prophylactic‐dose anticoagulation, and separately with in‐hospital aspirin compared to no antiplatelet therapy, in a large, retrospective study of 2785 hospitalized adult COVID‐19 patients. In this analysis, we established two separate, nested cohorts of patients (a) who received intermediate‐ or prophylactic‐dose anticoagulation (“anticoagulation cohort”, N = 1624), or (b) who were not on home antiplatelet therapy and received either in‐hospital aspirin or no antiplatelet therapy (“aspirin cohort”, N = 1956). To minimize bias and adjust for confounding factors, we incorporated propensity score matching and multivariable regression utilizing various markers of illness severity and other patient‐specific covariates, yielding treatment groups with well‐balanced covariates in each cohort. The primary outcome was cumulative incidence of in‐hospital death. Among propensity score‐matched patients in the anticoagulation cohort (N = 382), in a multivariable regression model, intermediate‐ compared to prophylactic‐dose anticoagulation was associated with a significantly lower cumulative incidence of in‐hospital death (hazard ratio 0.518 [0.308–0.872]). Among propensity‐score matched patients in the aspirin cohort (N = 638), in a multivariable regression model, in‐hospital aspirin compared to no antiplatelet therapy was associated with a significantly lower cumulative incidence of in‐hospital death (hazard ratio 0.522 [0.336–0.812]). In this propensity score‐matched, observational study of COVID‐19, intermediate‐dose anticoagulation and aspirin were each associated with a lower cumulative incidence of in‐hospital death.

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  1. ScreenIT

    SciScore for 10.1101/2021.01.12.21249577: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Patients, data collection, and variables: Institutional Review Board approval was obtained for this study; an approved Data Use Agreement between institutions permitted analysis.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    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 several limitations, beyond its retrospective nature. Overall provider adherence to our institution’s COVID-19 treatment guidelines was subject to provider preference, although many of the confounding factors that would have resulted from such bias were accounted for through our use of propensity score matching and multivariable regression analysis. Heterogeneity in the number of doses of intermediate-dose anticoagulation or aspirin that each patient received during their hospitalization may have biased our analysis against the detection of some significant associations by including patients in the intervention group who received limited exposure to the intervention. A possible improvement in clinical outcomes of hospitalized patients with COVID-19 over time could have biased some of our findings, although in our analysis of patients in the aspirin cohort admitted after May 18, a significant reduction in in-hospital mortality with aspirin use was still observed despite the later, shortened timeframe of the specific study population analyzed. We did not examine other COVID-19 therapies that patients may have received and did not examine VTE rates, as only a small percentage of patients in our hospital system underwent VTE-specific imaging in order to limit excess healthcare worker exposure to COVID-19. In summary, in our large, observational study of hospitalized patients with COVID-19, using propensity score matching and multivariable regression analyses, we obs...

    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

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  2. Version published to 10.1002/ajh.26102
  3. Version published to 10.1101/2021.01.12.21249577v1 on medRxiv