title: Clopidogrel effect on platelet reactivity in patients with stent thrombosis: results of the CREST Study.
abstract: OBJECTIVE
  We investigated whether patients who suffered subacute stent thrombosis (SAT) have higher post-treatment reactivity than those who do not encounter stent thrombosis.
  
  
  BACKGROUND
  High post-treatment platelet reactivity has been reported after coronary stenting after clopidogrel therapy and may be an important factor in the occurrence of SAT.
  
  
  METHODS
  We identified patients with SAT treated at two tertiary care centers over a 1.5-year period. Light transmittance aggregation induced by adenosine diphosphate (ADP) and arachidonic acid, total and activated glycoprotein (GP) IIb/IIIa after stimulation with ADP, and vasodilator-stimulated phosphoprotein phosphorylation levels to measure P2Y12 receptor inhibition were determined (n = 20) and compared with an age-matched group of patients without SAT (n = 100). High post-treatment platelet reactivity was defined as >75th percentile ADP-induced aggregation in the group without SAT.
  
  
  RESULTS
  The SAT patients had higher mean platelet reactivity than those without SAT by all measurements (p < 0.05): 49 +/- 4% versus 33 +/- 2% for 5 micromol/l ADP-induced aggregation and 65 +/- 3% versus 51 +/- 2% for 20 micromol/l ADP-induced aggregation (p < 0.001), 69 +/- 5% versus 46 +/- 9% for P2Y12 reactivity ratio (p = 0.03), and 138 +/- 19 mean fluorescence intensity (MFI) versus 42 +/- 4 MFI for stimulated GP IIb/IIIa expression (p < 0.001). Of patients with SAT, 60% had high platelet reactivity.
  
  
  CONCLUSIONS
  High post-treatment platelet reactivity and incomplete P2Y12 receptor inhibition are risk factors for SAT. Measures to uniformly determine platelet reactivity after coronary stenting and treatment strategies to improve P2Y12 receptor inhibition in patients with high post-treatment platelet reactivity should be further investigated.
authors.affiliation: Sinai Center for Thrombosis Research, Baltimore, Maryland 21215, USA. pgurbel@lifebridgehealth.org
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gurbel
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Bliden
authors.forename: Waiel
authors.initials: W
authors.lastname: Samara
authors.forename: Jason A
authors.initials: JA
authors.lastname: Yoho
authors.forename: Kevin
authors.initials: K
authors.lastname: Hayes
authors.forename: Mulugeta Z
authors.initials: MZ
authors.lastname: Fissha
authors.forename: Udaya S
authors.initials: US
authors.lastname: Tantry
mesh_terms: D000368:Aged; D000077144:Clopidogrel; D023921:Coronary Stenosis / Q000628:therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects*; D015607:Stents / Q000009:adverse effects*; D013927:Thrombosis / Q000097:blood* / Q000209:etiology*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000077144:Clopidogrel; D013988:Ticlopidine