Anticoagulants and Antiplatelets in COVID-19: Impact on Survival and Thromboembolism Development

  1. Thomas Salmon
  2. Mitchell Titley
  3. Zaid Noori
  4. Mark Crosby
  5. Rajiv Sankaranarayanan

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Abstract

Background

Higher rates of venous and arterial thromboembolism have been noted in coronavirus disease-2019 (COVID-19). There has been limited research on the impact of anticoagulant and antiplatelet choice in COVID-19.

Methods

This was a single-centre retrospective cohort study of 933 patients with COVID-19 infection presenting between 01/02/2020 and 31/05/2020. Survival time at 90 days post-diagnosis and thromboembolism development were the measured outcomes.

Results

Of 933 total patients, mean age was 68 years and 54.4% were male. 297 (31.8%) did not survive at 90 days. A Cox proportional hazards model analysis found no statistically significant relationship between anticoagulant or antiplatelet choice and survival (p<0.05).

57 (6.3%) developed thromboembolism. Antiplatelet choice was not shown to have a statistically significant relationship with thromboembolism development. Warfarin and direct oral anticoagulant (DOAC) use did not have a statistically significant impact on thromboembolism development (p<0.05). Therapeutic low-molecular-weight heparin (LMWH) use was associated with increased thromboembolism risk (Odds ratio = 14.327, 95% CI 1.904 – 107.811, p = 0.010).

Conclusions

Antiplatelet choice was shown to have no impact on survival or thromboembolism development in COVID-19. Anticoagulant choice did not impact survival or thromboembolism development, aside from LMWH. Therapeutic LMWH use was associated with increased risk of thromboembolism. However, it should be noted that the sample size for patients using therapeutic LMWH was small (n=4), and there may be confounding variables affecting both LMWH use and thromboembolism development. These findings should be repeated with a larger sample of patients using therapeutic LMWH with additional adjustment for cofounding variables.

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  1. ScreenIT

    SciScore for 10.1101/2021.07.03.21254541: (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
    Statistical analysis was performed using SPSS version 27.0.1.0.
    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:
    Limitations of study: As noted previously, the population sizes for groups taking dual antiplatelets (n=7) and therapeutic LMWH (n=4) were small. As such, findings related to these treatment groups should be interpreted with caution until studied with larger populations. Regarding dual antiplatelets, it is notable that no patient on dual antiplatelet therapy developed thromboembolism, although this was not deemed to be statistically significant in multivariate analysis. This warrants further study with a larger population. As mentioned previously, there are no current clinical trials of dual antiplatelet therapy for thromboembolism prevention in COVID-19 [27]. It is also important to note that the dose of antiplatelet medication taken was not recorded. The vast majority were taking 75mg aspirin daily, 75mg clopidogrel daily, or 75mg of each. Whilst the impact of higher dose antiplatelet regimes in COVID-19 certainly warrant investigation, a retrospective cohort study is not a suitable study design due to the underlying indications for higher dose aspirin or clopidogrel. Patients on higher doses will likely have suffered recent ischaemic stroke or acute coronary syndrome, and as such the impact of antiplatelet therapy on mortality and thromboembolism risk will be overshadowed by the risk attributable to these recent events. There are no ongoing large scale randomised control trials of the impact of higher dose antiplatelet medication in COVID-19 [27]. On a smaller scale, the C...

    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.

  2. Version published to 10.1101/2021.07.03.21254541v1 on medRxiv