title: Detecting a thienopyridine effect by platelet reactivity assessment and its implications for risk stratification.
abstract: BACKGROUND
  On-treatment platelet reactivity (OTR) is a predictor of clinical outcomes in patients receiving thienopyridine therapy.
  
  
  OBJECTIVE
  To assess whether point-of-care platelet reactivity testing can discriminate between patients who have and have not received a thienopyridine.
  
  
  METHODS
  This was an analysis of a randomized, multicenter, pharmacodynamic trial. Subjects with coronary artery disease treated with aspirin were randomly assigned to clopidogrel 75 mg daily or prasugrel 10 mg daily for 7 days. Platelet reactivity assessment with the VerifyNow P2Y12 test was performed before study drug admistration and 24 h after the final dose. Optimal cut-offs for a detectable drug effect were identified by the use of receiver operating characteristic curve analysis.
  
  
  RESULTS
  A total of 54 subjects were enrolled and completed the study. The c-statistic for the identification of a thienopyridine effect was highly significant (0.93, P < 0.001), including for the clopidogrel and prasugrel groups considered separately (P < 0.001 for both). The optimal cut-off was < 213 P2Y12 reaction units (PRU), which provided a sensitivity of 80% and a specificity of 98%. This cut-off provided a sensitivity of 58% and a specificity of 100% for a clopidogrel effect, and a sensitivity of 100% and specificity of 96% for a prasugrel effect.
  
  
  CONCLUSIONS
  OTR of < 213 PRU is highly specific for exposure to either clopidogrel or prasugrel. This may be useful in the management of thienoypridine-treated patients who require surgery. Furthermore, this diagnostic cut-off is similar to levels of OTR that have been associated with ischemic events in thienopyridine-treated patients, supporting the contention that a lack of drug effect is the mechanistic basis for the prognostic relationship between OTR and clinical outcomes.
authors.affiliation: Scripps Clinic and Scripps Translational Science Institute, La Jolla, CA, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Price
authors.forename: B A
authors.initials: BA
authors.lastname: Baker
authors.forename: J A
authors.initials: JA
authors.lastname: Jakubowski
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: D E
authors.initials: DE
authors.lastname: Heiselman
authors.forename: D J
authors.initials: DJ
authors.lastname: Angiolillo
mesh_terms: D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage*; D015539:Platelet Activation; D019095:Point-of-Care Systems; D000068799:Prasugrel Hydrochloride; D011725:Pyridines / Q000008:administration & dosage* / Q000737:chemistry; D012372:ROC Curve; D058925:Receptors, Purinergic P2Y12 / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013876:Thiophenes / Q000008:administration & dosage*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C548576:P2RY12 protein, human; D010879:Piperazines; D011725:Pyridines; D058925:Receptors, Purinergic P2Y12; D013876:Thiophenes; C446540:thienopyridine; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine; D001241:Aspirin
keywords: clopidogrel; platelet aggregation; platelet aggregation inhibitors; platelet function tests; prasugrel; thienopyridine