title: Determination of cut-off levels for on-clopidogrel platelet aggregation based on functional CYP2C19 gene variants in patients undergoing elective percutaneous coronary intervention.
abstract: BACKGROUND
  Carriers of reduced-function CYP2C19 allele on antiplatelet therapy show diminished platelet inhibition and higher rate of clinical risk. The purpose of this study was to determine cut-off levels of VerifyNow P2Y12 system associated with effective inhibition of on-clopidogrel platelet aggregation to predict carriers of CYP2C19 reduced-function allele among patients undergoing percutaneous coronary intervention (PCI).
  
  
  METHODS
  We enrolled 202 consecutive patients with stable coronary artery disease (CAD) undergoing PCI and treated with clopidogrel. All patients underwent CYP2C19 genotyping and measurement of residual platelet aggregation by VerifyNow system.
  
  
  RESULTS
  Carriers of CYP2C19 reduced-function allele constituted 131 (65%) of 202 CAD patients. Platelet inhibition measured by P2Y12 reaction units (PRU) and %inhibition was diminished in carriers compared with noncarriers (PRU: 290.0±81.2 vs 217.6±82.4, p<0.001, %inhibition: 17.9±17.8 vs 35.5±22.8, p<0.001, respectively). Multiple logistic regression analysis identified PRU and %inhibition as significant predictors of carrier state [odds ratio (OR) 4.95; 95% confidence interval (95%CI): 2.49 to 9.85; p<0.001, OR 5.55; 95%CI: 2.80 to 10.99; p<0.001, respectively]. Receiver-operating characteristic analysis showed that PRU and %inhibition were significant predictors of carrier state [area under the curve (AUC) 0.736 (95%CI: 0.664 to 0.808; p<0.001), AUC 0.727 (95%CI: 0.651 to 0.803; p<0.001), respectively]. The cut-off levels of PRU and %inhibition were 256 and 26.5% for the identification of carriers.
  
  
  CONCLUSIONS
  Our results suggested that the cut-off levels of PRU and %inhibition to discriminate carriers of CYP2C19 reduced-function allele from noncarriers are potentially useful clinically to provide optimal clopidogrel therapy in patients with stable CAD undergoing PCI.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Takamichi
authors.initials: T
authors.lastname: Ono
authors.forename: Koichi
authors.initials: K
authors.lastname: Kaikita
authors.forename: Seiji
authors.initials: S
authors.lastname: Hokimoto
authors.forename: Satomi
authors.initials: S
authors.lastname: Iwashita
authors.forename: Koichiro
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Eiji
authors.initials: E
authors.lastname: Horio
authors.forename: Koji
authors.initials: K
authors.lastname: Sato
authors.forename: Kenichi
authors.initials: K
authors.lastname: Tsujita
authors.forename: Tomohide
authors.initials: T
authors.lastname: Abe
authors.forename: Mariko
authors.initials: M
authors.lastname: Deguchi
authors.forename: Shinji
authors.initials: S
authors.lastname: Tayama
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sumida
authors.forename: Seigo
authors.initials: S
authors.lastname: Sugiyama
authors.forename: Hiroshige
authors.initials: H
authors.lastname: Yamabe
authors.forename: Sunao
authors.initials: S
authors.lastname: Nakamura
authors.forename: Kazuko
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015906:Angioplasty, Balloon, Coronary / Q000379:methods*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001241:Aspirin / Q000627:therapeutic use; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine; D001241:Aspirin