Platelet function/reactivity testing and prediction of risk of recurrent vascular events and outcomes after TIA or ischaemic stroke: systematic review and meta-analysis

Lim ST 1 , Thijs V 2 , Murphy SJX 1 , Fernandez-Cadenas I 3 , Montaner J 4 , Offiah C 1 Show all authors , Marquardt L 5 , Kelly PJ 6 , Bath PM 7 , Lim SY 8 , Ford GA 9 , Norrving B 10 , Cox D 11 , Prodan CI 12 , Barber PA 13 , Werring DJ 14 , Perry R 14 , Zgaga L 15 , Dawson J 16 , McCabe DJH 17

Affiliations 

  • 1 Department of Neurology, The Adelaide and Meath Hospital, Dublin, Incorporating the National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland
  • 2 Department of Neurology, Austin Health and Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg, Victoria, Australia
  • 3 Institut de Recerca Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
  • 4 Neurovascular Research Laboratory, Vall d'Hebron Institute of Research (VHIR), Barcelona, Spain
  • 5 Department of Neurology, Asklepios Klinik Wandsbek, Hamburg, Germany
  • 6 Neurovascular Clinical Science Unit, Mater University Hospital, University College Dublin, Dublin, Ireland
  • 7 Stroke Trials Unit, University of Nottingham, Nottingham, UK
  • 8 Faculty of Health and Medical Sciences, Taylor's University School of Medicine, Sungai Buloh, Malaysia
  • 9 University of Oxford, Oxford, UK
  • 10 Department of Clinical Sciences Lund, Neurology, Lund University, Lund, Sweden
  • 11 Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland
  • 12 Department of Neurology, University of Oklahoma Health Sciences Center and VA Medical Center, Oklahoma, USA
  • 13 Department of Clinical Neurosciences, University of Calgary, Calgary, Canada
  • 14 Department of Brain Repair and Rehabilitation, Stroke Research Centre, UCL Queen Square Institute of Neurology, London, UK
  • 15 Department of Public Health and Primary Care, Trinity College Dublin, University of Dublin, Dublin, Ireland
  • 16 Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
  • 17 Department of Neurology, The Adelaide and Meath Hospital, Dublin, Incorporating the National Children's Hospital (AMNCH)/Tallaght University Hospital, Dublin, Ireland. [email protected]
J Neurol, 2020 Oct;267(10):3021-3037.
PMID: 32518978 DOI: 10.1007/s00415-020-09932-y

Abstract

BACKGROUND: The prevalence of ex vivo 'high on-treatment platelet reactivity (HTPR)' and its relationship with recurrent vascular events/outcomes in patients with ischaemic cerebrovascular disease (CVD) is unclear.

METHODS: A systematic review and meta-analysis was performed in accordance with the PRISMA statement. MEDLINE, EMBASE and Cochrane Library were searched for completed manuscripts until May 2019 on TIA/ischaemic stroke patients, ≥ 18 years, treated with commonly-prescribed antiplatelet therapy, who had platelet function/reactivity testing and prospective follow-up data on recurrent stroke/TIA, myocardial infarction, vascular death or other cerebrovascular outcomes. Data were pooled using random-effects meta-analysis. Primary outcome was the composite risk of recurrent stroke/TIA, myocardial infarction or vascular death. Secondary outcomes were recurrent stroke/TIA, severe stroke (NIHSS > 16) or disability/impairment (modified Rankin scale ≥ 3) during follow-up.

RESULTS: Antiplatelet-HTPR prevalence was 3-65% with aspirin, 8-56% with clopidogrel and 1.8-35% with aspirin-clopidogrel therapy. Twenty studies (4989 patients) were included in our meta-analysis. There was a higher risk of the composite primary outcome (OR 2.93, 95% CI 1.90-4.51) and recurrent ischaemic stroke/TIA (OR 2.43, 95% CI 1.51-3.91) in patients with vs. those without 'antiplatelet-HTPR' on any antiplatelet regimen. These risks were also more than twofold higher in patients with vs. those without 'aspirin-HTPR' and 'dual antiplatelet-HTPR', respectively. Clopidogrel-HTPR status did not significantly predict outcomes, but the number of eligible studies was small. The risk of severe stroke was higher in those with vs. without antiplatelet-HTPR (OR 2.65, 95% CI 1.00-7.01).

DISCUSSION: Antiplatelet-HTPR may predict risks of recurrent vascular events/outcomes in CVD patients. Given the heterogeneity between studies, further prospective, multi-centre studies are warranted.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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