title: Association of cytochrome P450 2C19*2 polymorphism with clopidogrel response variability and cardiovascular events in Koreans treated with drug-eluting stents.
abstract: BACKGROUND
  Although East Asians carry the cytochrome P450 (CYP) 2C19*2 allele more frequently than do Caucasians, the impact of the CYP2C19*2 allele on clopidogrel pharmacodynamics and clinical outcomes is unknown.
  
  
  OBJECTIVE
  To evaluate the effect of CYP2C19 variants on clopidogrel pharmacodynamics and long-term prognosis in East Asian patients with drug-eluting stents (DES).
  
  
  METHODS
  DES-treated patients taking dual antiplatelet therapy were enrolled from a Korean multicentre genetic registry. The CYP2C19*2 allele was genotyped using the Taqman method (n=2146), and on-treatment platelet reactivity was measured with the VerifyNow P2Y12 assay (n=1415).
  
  
  RESULTS
  1011 patients (47%) carried at least one CYP2C19*2 allele. The mean on-treatment platelet reactivity was significantly higher in carriers than in non-carriers (250±76 vs 231±83 P2Y12 reaction unit, p<0.001). For up to 12 months' follow-up, the composite of cardiovascular death, non-fatal myocardial infarction and stent thrombosis was significantly higher in carriers of the CYP2C19*2 allele than non-carriers (2.0% vs 0.8%, p=0.02). On landmark analysis, there was no difference in clinical outcome after 12 months between the groups.
  
  
  CONCLUSIONS
  The CYP2C19*2 genetic variant may be associated with worse outcome in Korean patients treated exclusively with DES and dual-antiplatelet therapy due to a significant increase in cardiac death, myocardial infarction or stent thrombosis.
authors.affiliation: Department of Internal Medicine, Cardiovascular Center, Seoul National University Hospital, 28 Yongong-dong, Chongno-gu, Seoul, Korea.
authors.forename: Il-Young
authors.initials: IY
authors.lastname: Oh
authors.forename: Kyung Woo
authors.initials: KW
authors.lastname: Park
authors.forename: Si-Hyuk
authors.initials: SH
authors.lastname: Kang
authors.forename: Jin Joo
authors.initials: JJ
authors.lastname: Park
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Na
authors.forename: Hyun-Jae
authors.initials: HJ
authors.lastname: Kang
authors.forename: Bon-Kwon
authors.initials: BK
authors.lastname: Koo
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Jeong
authors.forename: Jin-Yong
authors.initials: JY
authors.lastname: Hwang
authors.forename: Choong Hwan
authors.initials: CH
authors.lastname: Kwak
authors.forename: Yongwhi
authors.initials: Y
authors.lastname: Park
authors.forename: Seok-Jae
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Young-Guk
authors.initials: YG
authors.lastname: Ko
authors.forename: Dong Jik
authors.initials: DJ
authors.lastname: Shin
authors.forename: Yangsoo
authors.initials: Y
authors.lastname: Jang
authors.forename: Hyo-Soo
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000628:therapy; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D054855:Drug-Eluting Stents; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D012042:Registries; D056910:Republic of Korea; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / 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