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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, Soon Tjin; Thijs, Vincent; Murphy, Stephen J. X.; Fernandez-Cadenas, Israel; Montaner, Joan; Offiah, Chika; Marquardt, Lars; Kelly, Peter J.; Bath, Philip M.; Lim, Su-Yin; Ford, Gary A.; Norrving, Bo; Cox, Dermot; Prodan, Calin I.; Barber, Philip A.; Werring, David J.; Perry, Richard; Zgaga, Lina; Dawson, Jesse; McCabe, Dominick J. H.

Authors

Soon Tjin Lim

Vincent Thijs

Stephen J. X. Murphy

Israel Fernandez-Cadenas

Joan Montaner

Chika Offiah

Lars Marquardt

Peter J. Kelly

PHILIP BATH philip.bath@nottingham.ac.uk
Stroke Association Professor of Stroke Medicine

Su-Yin Lim

Gary A. Ford

Bo Norrving

Dermot Cox

Calin I. Prodan

Philip A. Barber

David J. Werring

Richard Perry

Lina Zgaga

Jesse Dawson

Dominick J. H. McCabe



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.

Citation

Lim, S. T., Thijs, V., Murphy, S. J. X., Fernandez-Cadenas, I., Montaner, J., Offiah, C., …McCabe, D. J. H. (2020). Platelet function/reactivity testing and prediction of risk of recurrent vascular events and outcomes after TIA or ischaemic stroke: systematic review and meta-analysis. Journal of Neurology, https://doi.org/10.1007/s00415-020-09932-y

Journal Article Type Article
Acceptance Date May 19, 2020
Online Publication Date Jun 9, 2020
Publication Date Jun 9, 2020
Deposit Date Jun 12, 2020
Publicly Available Date Jun 10, 2021
Journal Journal of Neurology
Print ISSN 0340-5354
Electronic ISSN 1432-1459
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
DOI https://doi.org/10.1007/s00415-020-09932-y
Keywords Platelet function/on-treatment platelet reactivity, Transient ischaemic attack, Ischaemic stroke, Systematic review, Meta-analysis
Public URL https://nottingham-repository.worktribe.com/output/4630807
Publisher URL https://link.springer.com/article/10.1007%2Fs00415-020-09932-y
Additional Information This is a post-peer-review, pre-copyedit version of an article published in Journal of Neurology. The final authenticated version is available online at: http://dx.doi.org/10.1007/s00415-020-09932-y

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