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 metaanalysis. 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 (4,989 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.

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