title: Relationship between clopidogrel-induced platelet P2Y12 inhibition and stent thrombosis or myocardial infarction after percutaneous coronary intervention-a case-control study.
abstract: BACKGROUND
  Insufficient platelet inhibition is a major determinant of stent thrombosis (STh), although the etiology is multifactorial. On-clopidogrel platelet reactivity was investigated in patients with previous angiographically confirmed STh, myocardial infarction (MI), and controls.
  
  
  METHODS
  Using the Swedish Coronary Angiography and Angioplasty Registry, we identified patients with angiographically confirmed STh (n = 48) or MI (n = 30) while on dual antiplatelet therapy within 6 months of percutaneous coronary intervention (PCI) and matched control patients (n = 78). On-clopidogrel platelet reactivity was measured with VerifyNow P2Y12 and vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay.
  
  
  RESULTS
  The mean P2Y12 reaction units (PRU) was higher (246.8 ± 75.9 vs 200.0 ± 82.7, P = .001) in STh patients compared with controls. The optimal cutoff for STh was 222 PRU or higher (area under the curve 0.69, P < .0001) in a receiver operating characteristics (ROC) analysis. The cutoff level resulted in 70.2% sensitivity and 67.3% specificity. There was no significant difference in mean PRU but a higher device-reported percent inhibition (45.1 ± 23.8 vs 32.1 ± 23.2, P = .04) in patients with MI compared with controls. Results with the VASP phosphorylation assay were not related to the occurrence of STh or MI.
  
  
  CONCLUSIONS
  STh was associated with high on-clopidogrel platelet reactivity measured with VerifyNow (cutoff level of PRU ≥222) but spontaneous MI in stented patients on clopidogrel treatment was not. There was, however, a substantial overlap in on-clopidogrel platelet reactivity between patients with and without on-treatment STh questioning the clinical use of platelet function testing to identify patients at high risk for STh.
authors.affiliation: Uppsala Clinical Research Center, Department of Medical Sciences, Cardiology, Uppsala University, Sweden. christoph.varenhorst@ucr.uu.se
authors.forename: Christoph
authors.initials: C
authors.lastname: Varenhorst
authors.forename: Sasha
authors.initials: S
authors.lastname: Koul
authors.forename: David
authors.initials: D
authors.lastname: Erlinge
authors.forename: Bo
authors.initials: B
authors.lastname: Lagerqvist
authors.forename: Agneta
authors.initials: A
authors.lastname: Siegbahn
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.forename: Stefan
authors.initials: S
authors.lastname: James
mesh_terms: D054058:Acute Coronary Syndrome / Q000175:diagnosis; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000379:methods*; D000077144:Clopidogrel; D017023:Coronary Angiography; D003328:Coronary Thrombosis / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011475:Prosthesis Failure; D058925:Receptors, Purinergic P2Y12 / Q000097:blood / Q000187:drug effects*; D012189:Retrospective Studies; D015607:Stents; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D013988:Ticlopidine