title: Comparison of the effect of CYP2C19 polymorphism on clinical outcome between acute coronary syndrome and stable angina.
abstract: OBJECTIVE
  CYP2C19 polymorphism modulates platelet reactivity in coronary artery disease patients with stent implants. However, the impact of the CYP2C19 genotype on clopidogrel response and clinical outcome has not been fully understood to date.
  
  
  METHODS
  We enrolled 518 consecutive patients with acute coronary syndrome (ACS) (n=214) and stable angina (SA) (n=304). All patients received stent implants followed by dual antiplatelet therapy of aspirin and clopidogrel. We determined CYP2C19 phenotype, measured platelet reactivity, and assessed the risk of cardiovascular events.
  
  
  RESULTS
  During a median follow-up of 894 days, the rate of cardiovascular events was higher in patients of the ACS group than the SA group (ACS: 20.1%, SA: 12.5%, p=0.015). The mean platelet reactivity was significantly higher in the CYP2C19 loss-of-function allele carriers of the two groups (ACS, non-carriers: 3909±1836AUmin, carriers: 4854±1594AUmin, respectively, p<0.01; SA, 3606±1579AUmin, 4381±1373AUmin, ±SD, p<0.01). In the ACS group, cardiovascular events were higher in the loss-of-function allele carriers (24.6%) versus non-carriers (11.1%, p<0.05), but no such difference was noted in the SA group (carriers: 14.8%; non-carriers: 7.9%, p=0.078). Furthermore, landmark analysis from 30 days did not show differences in ACS group (carriers: 14.8%, non-carriers: 11.1%, p=0.315). Multivariate Cox proportional hazards analysis identified the presence of loss-of-function allele as an independent predictor of cardiovascular events (hazard ratio, 2.1, 95% CI, 1.194-3.587, p=0.010).
  
  
  CONCLUSIONS
  The impact of CYP2C19 loss-of-function gene on clinical outcome is more powerful in early phase of ACS compared with SA.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Arima
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan. Electronic address: shokimot@kumamoto-u.ac.jp.
authors.forename: Seiji
authors.initials: S
authors.lastname: Hokimoto
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Akasaka
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Mizobe
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kaikita
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Oniki
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000235:genetics; D000368:Aged; D000483:Alleles; D060050:Angina, Stable / Q000188:drug therapy* / Q000235:genetics; D001241:Aspirin / Q000627:therapeutic use; D001792:Blood Platelets; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D054855:Drug-Eluting Stents; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine; D001241:Aspirin
keywords: Antiplatelet therapy; CYP2C19; Clopidogrel; Percutaneous coronary intervention; Polymorphism