title: High on-treatment platelet reactivity on commonly prescribed antiplatelet agents following transient ischaemic attack or ischaemic stroke: results from the Trinity Antiplatelet Responsiveness (TRAP) study.
abstract: OBJECTIVE
  The prevalence of ex vivo 'high on-treatment platelet reactivity' (HTPR) to antiplatelet regimens in patients with ischaemic cerebrovascular disease (CVD) is uncertain.
  
  
  METHODS
  HTPR was assessed with PFA-100 collagen-epinephrine (C-EPI) and collagen-ADP (C-ADP) cartridges. Platelet activation (CD62P, CD63 and leucocyte-platelet complex formation) was assessed with whole-blood flow cytometry. Patients were assessed at baseline [≤ 4 weeks of transient ischaemic attack (TIA) or ischaemic stroke], and at 14 days and ≥ 90 days after changing treatment from (i) no medication to aspirin monotherapy (N = 26) or (ii) aspirin to clopidogrel monotherapy (N = 22). HTPR was defined in a novel, 'longitudinal fashion' as failure to prolong relevant closure times compared with the patient's 'baseline value' before he/she underwent an antiplatelet change by more than twice the coefficient of variation of the assay.
  
  
  RESULTS
  (i) C-EPI closure times increased at 14 days and 90 days after commencing aspirin (P = 0.002); 24% at 14 days and 18% at 90 days demonstrated HTPR on aspirin. (ii) C-ADP closure times increased at 14 days (P = 0.001) but not 90 days (P = 0.09) after changing from aspirin to clopidogrel; 41% at 14 days, and 35% at 90 days demonstrated HTPR on clopidogrel. Platelet activation was unaffected by aspirin (P = 0.09). The percentage neutrophil-platelet complexes decreased at 14 days (P = 0.02), but this reduction was not maintained 90 days after changing to clopidogrel (P = 0.3). No patient had a recurrent vascular event during prospective follow-up.
  
  
  CONCLUSIONS
  Longitudinal definitions of HTPR in patients with ischaemic CVD who are undergoing a change in antiplatelet therapy have the potential to provide more clinically meaningful information than traditional 'cross-sectional definitions' of HTPR which are usually based on the comparison of patients' values with those in healthy controls. Using our novel, longitudinal definition of HTPR, the PFA-100 could be used to monitor ex vivo responsiveness to aspirin, and larger, prospective studies are warranted to assess the clinical predictive value of this and other platelet function tests in patients with ischaemic CVD.
authors.affiliation: Department of Neurology, Adelaide and Meath Hospital, Dublin, incorporating the National Children's Hospital, Trinity College Dublin, Dublin, Ireland.
authors.forename: W O
authors.initials: WO
authors.lastname: Tobin
authors.forename: J A
authors.initials: JA
authors.lastname: Kinsella
authors.forename: T
authors.initials: T
authors.lastname: Coughlan
authors.forename: D R
authors.initials: DR
authors.lastname: Collins
authors.forename: D
authors.initials: D
authors.lastname: O'Neill
authors.forename: R P
authors.initials: RP
authors.lastname: Murphy
authors.forename: B
authors.initials: B
authors.lastname: Egan
authors.forename: S
authors.initials: S
authors.lastname: Tierney
authors.forename: T M
authors.initials: TM
authors.lastname: Feeley
authors.forename: D J H
authors.initials: DJ
authors.lastname: McCabe
mesh_terms: D000368:Aged; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D000077144:Clopidogrel; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D002546:Ischemic Attack, Transient / Q000097:blood / Q000276:immunology / Q000503:physiopathology*; D007962:Leukocytes / Q000502:physiology; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism; D010865:Pilot Projects; D015539:Platelet Activation / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D010979:Platelet Function Tests; D020521:Stroke / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D060149:Tetraspanin 30 / Q000378:metabolism; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C554586:CD63 protein, human; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D060149:Tetraspanin 30; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin