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Relationship between ‘on-treatment platelet reactivity’, shear stress, and micro-embolic signals in asymptomatic and symptomatic carotid stenosis

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Abstract

Background

Assessment of ‘high on-treatment platelet reactivity (HTPR)’ could enhance understanding of the pathophysiology of first or recurrent vascular events in carotid stenosis patients on antiplatelet therapy.

Methods

This prospective, multi-centre study assessed antiplatelet–HTPR status and its relationship with micro-emboli signals (MES) in asymptomatic vs. symptomatic ≥ 50–99% carotid stenosis. Platelet function/reactivity was assessed under ‘moderately high shear stress’ with the PFA-100® and ‘low shear stress’ with VerifyNow® and Multiplate® analysers. Bilateral 1-h transcranial Doppler ultrasound of the middle cerebral arteries classified patients as MES + ve or MES − ve.

Results

Data from 34 asymptomatic patients were compared with 43 symptomatic patients in the ‘early phase’ (≤ 4 weeks) and 37 patients in the ‘late phase’ (≥ 3 months) after TIA/ischaemic stroke. Median daily aspirin doses were higher in early symptomatic (225 mg; P < 0.001), but not late symptomatic (75 mg; P = 0.62) vs. asymptomatic patients (75 mg). There was a lower prevalence of aspirin–HTPR in early (28.6%; P = 0.028), but not late symptomatic (38.9%; P = 0.22) compared with asymptomatic patients (56.7%) on the PFA-100®, but not on the VerifyNow® or Multiplate® (P ≤ 0.53). Early symptomatic patients had a higher prevalence of aspirin–HTPR on the PFA-100® (28.6%) vs. VerifyNow® (9.5%; P = 0.049), but not Multiplate® assays (11.9%, P = 0.10). There was no difference in aspirin–HTPR prevalence between any symptomatic vs. asymptomatic MES + ve or MES − ve subgroup.

Discussion

Recently symptomatic moderate–severe carotid stenosis patients had a lower prevalence of aspirin–HTPR than their asymptomatic counterparts on the PFA-100®, likely related to higher aspirin doses. The prevalence of antiplatelet–HTPR was positively influenced by higher shear stress levels, but not MES status.

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Acknowledgements

All HEIST collaborators qualified for authorship as they contributed to data acquisition or study design, and all critically appraised the manuscript for important intellectual content. Dr Murphy’s research was funded by the Trinity College Dublin Innovation Bursary, the Meath Foundation, Ireland, Joint IICN/Merck Serono Fellowship in Neuroscience, The Vascular Neurology Research Foundation, Ireland, and by an unrestricted educational grant from Bayer HealthCare Ireland, and Verum Diagnostica, GmbH. Dr. Lim’s research was funded by the Meath Foundation, Ireland, The Irish Institute of Clinical Neuroscience (IICN)/Novartis Ireland Fellowship Grant, The Irish Heart Foundation Stroke Prevention Bursary, and by unrestricted educational grant funding from Biogen Idec Ireland. None of the above charities or funding bodies had any influence on design or conduct of this study, or had any influence on the decision to submit the final manuscript for publication. All authors critically reviewed and approved the final submitted manuscript. The manuscript has not been submitted elsewhere and has not been published elsewhere in whole or in part, except as an abstract.

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Authors and Affiliations

  1. Vascular Neurology Research Foundation, C/O Department of Neurology, The Adelaide and Meath Hospital, Dublin, Incorporating the National Children’s Hospital (AMNCH)/Tallaght University Hospital, Tallaght, Dublin 24, Ireland

    D. J. H. McCabe

  2. Department of Neurology, AMNCH/Tallaght University Hospital, Dublin, Ireland

    S. J. X. Murphy, S. T. Lim, S. M. Murphy, R. A. Walsh & D. J. H. McCabe

  3. Department of Vascular Surgery, AMNCH/Tallaght University Hospital, Dublin, Ireland

    S. Tierney, B. Egan & T. M. Feeley

  4. Age-Related Health Care Department, AMNCH/Tallaght University Hospital, Dublin, Ireland

    D. R. Collins, T. Coughlan & D. O’Neill

  5. Stroke Service, AMNCH/Tallaght University Hospital, Dublin, Ireland

    S. J. X. Murphy, S. T. Lim, S. M. Murphy, D. R. Collins, T. Coughlan, D. O’Neill & D. J. H. McCabe

  6. Dublin Midlands Hospital Group, Dublin, Ireland

    T. M. Feeley

  7. Department of Neurology, St Vincent’s University Hospital, University College Dublin, Dublin, Ireland

    J. A. Kinsella

  8. Department of Medicine for the Elderly/Stroke Service, St. James’s Hospital/Trinity College Dublin, Dublin, Ireland

    J. A. Harbison

  9. Department of Vascular Surgery, St. James’s Hospital/Trinity College Dublin, Dublin, Ireland

    P. Madhavan, S. M. O’Neill & M. P. Colgan

  10. Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland

    D. Cox & N. Moran

  11. Department of Vascular Surgery, University Department of Surgery, Royal Free Hampstead NHS Trust, London, UK

    G. Hamilton

  12. Department of Radiology, Centre for Advanced Medical Imaging, St. James’s Hospital/Trinity College Dublin, Dublin, Ireland

    J. F. Meaney

  13. Department of Clinical Neurosciences, Royal Free Campus, UCL Queen Square Institute of Neurology, London, UK

    D. J. H. McCabe

  14. Irish Centre for Vascular Biology, Dublin, Ireland

    D. Cox, N. Moran & D. J. H. McCabe

  15. Stroke Clinical Trials Network Ireland, Dublin, Ireland

    D. J. H. McCabe

  16. Academic Unit of Neurology, School of Medicine, Trinity College Dublin, Dublin, Ireland

    S. M. Murphy, R. A. Walsh & D. J. H. McCabe

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Corresponding author

Correspondence to D. J. H. McCabe.

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This study been approved by the local ethics committee and has, therefore, been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All persons gave their written informed consent prior to their inclusion in the study. The authors declare that they have no conflicts of interest.

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Murphy, S.J.X., Lim, S.T., Kinsella, J.A. et al. Relationship between ‘on-treatment platelet reactivity’, shear stress, and micro-embolic signals in asymptomatic and symptomatic carotid stenosis. J Neurol 267, 168–184 (2020). https://doi.org/10.1007/s00415-019-09550-3

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  • DOI: https://doi.org/10.1007/s00415-019-09550-3

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