Evaluation of antithrombotic use and COVID-19 outcomes in a nationwide atrial fibrillation cohort

  1. Alex Handy
  2. Amitava Banerjee
  3. Angela M Wood
  4. Caroline Dale
  5. Cathie L M Sudlow
  6. Christopher Tomlinson
  7. Daniel Bean
  8. Johan H Thygesen
  9. Mehrdad A Mizani
  10. Michail Katsoulis
  11. Rohan Takhar
  12. Sam Hollings
  13. Spiros Denaxas
  14. Venexia Walker
  15. Richard Dobson
  16. Reecha Sofat

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Abstract

To evaluate antithrombotic (AT) use in individuals with atrial fibrillation (AF) and at high risk of stroke (CHA 2 DS 2 -VASc score ≥2) and investigate whether pre-existing AT use may improve COVID-19 outcomes.

Methods

Individuals with AF and CHA 2 DS 2 -VASc score ≥2 on 1 January 2020 were identified using electronic health records for 56 million people in England and were followed up until 1 May 2021. Factors associated with pre-existing AT use were analysed using logistic regression. Differences in COVID-19-related hospitalisation and death were analysed using logistic and Cox regression in individuals with pre-existing AT use versus no AT use, anticoagulants (AC) versus antiplatelets (AP), and direct oral anticoagulants (DOACs) versus warfarin.

Results

From 972 971 individuals with AF (age 79 (±9.3), female 46.2%) and CHA 2 DS 2 -VASc score ≥2, 88.0% (n=856 336) had pre-existing AT use, 3.8% (n=37 418) had a COVID-19 hospitalisation and 2.2% (n=21 116) died, followed up to 1 May 2021. Factors associated with no AT use included comorbidities that may contraindicate AT use (liver disease and history of falls) and demographics (socioeconomic status and ethnicity). Pre-existing AT use was associated with lower odds of death (OR=0.92, 95% CI 0.87 to 0.96), but higher odds of hospitalisation (OR=1.20, 95% CI 1.15 to 1.26). AC versus AP was associated with lower odds of death (OR=0.93, 95% CI 0.87 to 0.98) and higher hospitalisation (OR=1.17, 95% CI 1.11 to 1.24). For DOACs versus warfarin, lower odds were observed for hospitalisation (OR=0.86, 95% CI 0.82 to 0.89) but not for death (OR=1.00, 95% CI 0.95 to 1.05).

Conclusions

Pre-existing AT use may be associated with lower odds of COVID-19 death and, while not evidence of causality, provides further incentive to improve AT coverage for eligible individuals with AF.

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  1. Version published to 10.1136/heartjnl-2021-320325
  2. ScreenIT

    SciScore for 10.1101/2021.09.03.21263023: (What is this?)

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

    Table 1: Rigor

    EthicsField Sample Permit: Analyses were conducted by approved researcher (AH) via secure remote access to the TRE.
    IRB: The North East-Newcastle and North Tyneside 2 research ethics committee provided ethical approval for the CVD-COVID-UK research programme (REC No 20/NE/0161).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    DOACs in mitral stenosis, prosthetic mechanical valves, antiphospholipid antibody syndrome) were included as they are still eligible for other AT sub-types (e.g. AP, warfarin).
    antiphospholipid
    suggested: None
    Software and Algorithms
    SentencesResources
    Data preparation was performed using Python 3.7 and Spark SQL (2.4.5) on Databricks Runtime 6.4 for Machine Learning with analysis performed using R version 4.0.3.
    Python
    suggested: (IPython, RRID:SCR_001658)

    Results from OddPub: Thank you for sharing your code and data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Strength and limitations: To our knowledge, this study is the largest scale evaluation of AT use to date. Routinely updated, linked, population-scale EHR datasets provide the statistical power to robustly analyse targeted sub-groups and control for a wide range of potential confounders. The prevalence of individuals with AF and CHA2DS2-VASc score>=2 in our cohort is similar to that observed in the Quality and Outcomes Framework[17] which provides an external validation for our dataset. All code is opensource and an updated nationwide evaluation can be rapidly created for future time points. The study does have limitations. Firstly, the reported associations do not demonstrate causality and residual confounding is unlikely to have been fully eliminated. For example, in-hospital treatment regimens were not analysed so differences in COVID-19 outcomes due to additional targeted anticoagulation regimens[28] or other medications such as dexamethasone[29] cannot be accounted for in our analysis. Whilst we attempted to mitigate confounding through careful cohort selection, covariates and propensity score adjustment, our study design does not control for all potential factors associated with the initiation of AT use which may influence COVID-19 outcomes. Lastly, exposure to AT medication was defined as one or more dispensed prescriptions (recorded in NHS BSA Dispensed Medicines) in the previous 6 months. Other studies have used different time periods and prescription frequency counts...

    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.

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  3. Version published to 10.1101/2021.09.03.21263023v1 on medRxiv