Combined anticoagulant and antiplatelet therapy is associated with an improved outcome in hospitalised patients with COVID-19: a propensity matched cohort study

  1. Kamal Matli
  2. Nibal Chamoun
  3. Aya Fares
  4. Victor Zibara
  5. Soad Al-Osta
  6. Rabih Nasrallah
  7. Pascale Salameh
  8. Jacques Mokhbat
  9. Georges Ghanem

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Abstract

COVID-19 is a respiratory disease that results in a prothrombotic state manifesting as thrombotic, microthrombotic and thromboembolic events. As a result, several antithrombotic modalities have been implicated in the treatment of this disease. This study aimed to identify if therapeutic anticoagulation (TAC) or concurrent use of antiplatelet and anticoagulants was associated with an improved outcome in this patient population.

Methods

A retrospective observational cohort study of adult patients admitted to a single university hospital for COVID-19 infection was performed. The primary outcome was a composite of in-hospital mortality, intensive care unit (ICU) admission or the need for mechanical ventilation. The secondary outcomes were each of the components of the primary outcome, in-hospital mortality, ICU admission, or the need for mechanical ventilation.

Results

242 patients were included in the study and divided into four subgroups: Therapeutic anticoagulation (TAC), prophylactic anticoagulation+antiplatelet (PACAP), TAC+antiplatelet (TACAP) and prophylactic anticoagulation (PAC) which was the reference for comparison. Multivariable Cox regression analysis and propensity matching were done and showed when compared with PAC, TACAP and TAC were associated with less in-hospital all-cause mortality with an adjusted HR (aHR) of 0.113 (95% CI 0.028 to 0.449) and 0.126 (95% CI 0.028 to 0.528), respectively. The number needed to treat in both subgroups was 11. Furthermore, PACAP was associated with a reduced risk of invasive mechanical ventilation with an aHR of 0.07 (95% CI 0.014 to 0.351). However, the was no statistically significant difference in the occurrence of major or minor bleeds, ICU admission or the composite outcome of in-hospital mortality, ICU admission or the need for mechanical ventilation.

Conclusion

The use of combined anticoagulant and antiplatelet agents or TAC alone in hospitalised patients with COVID-19 was associated with a better outcome in comparison to PAC alone without an increase in the risk of major and minor bleeds. Sufficiently powered randomised controlled trials are needed to further evaluate the safety and efficacy of combining antiplatelet and anticoagulants agents or using TAC in the management of patients with COVID-19 infection.

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  1. Version published to 10.1136/openhrt-2021-001785
  2. ScreenIT

    SciScore for 10.1101/2021.07.13.21260467: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Institutional Review Board Approval: This study was reviewed and approved by the Lebanese American University Institutional Review Board (IRB) (LAUMCRH.GG4.29/Jan/2021).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisMinimal sample size calculation: Given an alpha of 5% and 80% power with 9 independent variables in the Cox-proportional hazards model, a minimum of 226 patients would be necessary to fit a parsimonious model adjusting for confounding variables; this minimal sample size was calculated using the G*Power software.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Minimal sample size calculation: Given an alpha of 5% and 80% power with 9 independent variables in the Cox-proportional hazards model, a minimum of 226 patients would be necessary to fit a parsimonious model adjusting for confounding variables; this minimal sample size was calculated using the G*Power software.
    G*Power
    suggested: (G*Power, RRID:SCR_013726)
    Statistical Analysis: Data analysis was performed using SPSS.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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:
    Several limitations of this study should be mentioned. Given that this is a retrospective cohort study, association and not causality can be reported between the antithrombotic regimens and outcomes. The sample size was relatively small which makes it difficult to completely adjust for confounding and limits generalizability of the results. Despite efforts to control confounders by using different analytical strategies, some potential biases may have been disregarded, leading to a potential residual confounding. Data are based on the experience of a single center in Lebanon which prevents generalizability of our findings based on a potential selection bias. Furthermore, thrombotic events may have been underreported due to the strict isolation measures for covid-19, which may have led treating physicians to underuse imaging for appropriate diagnosis, generating a possible information bias. Strengths of the study include that it may be one of the first studies to examine the combination of therapies for the management of SARS COV-2 to prevent adverse outcomes. In addition, to adjust the analysis for significant variables a propensity matched multivariable cox regression model was employed. Lastly, hazards models that allow time to event analysis accounting for multiple outcomes were employed.

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

    IdentifierStatusTitle
    NCT04505774RecruitingAnti-thrombotics for Adults Hospitalized With COVID-19 (ACTI…
    NCT02735707RecruitingRandomized, Embedded, Multifactorial Adaptive Platform Trial…
    NCT04372589Active, not recruitingAntithrombotic Therapy to Ameliorate Complications of COVID-…

    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 10.1101/2021.07.13.21260467v1 on medRxiv