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

[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.
Dr. Lim’s research was funded by The Meath Foundation, The Irish Institute of Clinical Neuroscience/Novartis Ireland Fellowship Grant, The Vascular Neurology Research Foundation Ireland, the Irish Heart Foundation Stroke Prevention Bursary programme, and by an unrestricted educational grant from Biogen Idec, Ireland. Dr. Murphy’s research was funded by the Trinity College Dublin Innovation Bursary, The Meath Foundation, Joint Irish Institute of Clinical Neuroscience/Merck Serono Fellowship in Neuroscience Grant, The Vascular Neurology Research Foundation Ireland, and by an unrestricted educational grant from Bayer HealthCare, Ireland and Verum Diagnostica, GmbH. Dr Offiah’s Research is funded by The Meath Foundation and The Vascular Neurology Research Foundation Ireland and by an unrestricted educational grant from SINNOWA Medical Science & Technology Co., China. Prof Thijs’ research is supported by The Florey Institute of Neuroscience and Mental Health, which acknowledges support from the Victorian Government and funding from an Operational Infrastructure Support Grant. Prof Prodan’s research is supported by a United States Department of Veterans Affairs Merit Award (1I01CX000340). Prof Kelly is supported by grants from the Health Research Board Ireland. Prof Barber is supported by grants from the Canadian Institute of Health Research and the Heart and Stroke Foundation of Canada. Prof Werring receives research support from the Stroke Association and the British Heart Foundation. Prof Thijs has received personal fees for lectures and consulting fees from Bayer, Boehringer Ingelheim, BMS/Pfizer and Amgen. Prof. Bath is a Stroke Association Professor of Stroke Medicine and NIHR Senior Investigator, a non-executive Director of ‘Platelet Solutions Ltd.®, and owns 3 shares; he has received personal fees for consulting from DiaMedica, Moleac, Nestle, Sanofi and Phagenesis. Prof Werring has received honoraria for consulting and lectures from Bayer and Portola, and for consulting from Alnylam.