title: CYP2C19 poor metabolizer is associated with clinical outcome of clopidogrel therapy in acute myocardial infarction but not stable angina.
abstract: BACKGROUND
  More intensive platelet suppression is required in patients with acute myocardial infarction (AMI) than in those with stable angina because of differential platelet activation between AMI and stable angina. In this context, CYP2C19 genotype leading to reduced active metabolite formation may profoundly affect the clinical outcome of clopidogrel therapy in patients with AMI compared with those with stable angina.
  
  
  RESULTS
  Effects of CYP2C19 genotypes on the clinical outcome of clopidogrel therapy were evaluated in 2188 patients (532 patients with AMI and 1656 patients with stable angina) undergoing percutaneous coronary intervention. The primary clinical outcome was a composite of major adverse cardiac and cerebrovascular events defined as death from any cause, nonfatal myocardial infarction, or stroke during 1 year of clopidogrel therapy. Compared with extensive metabolizer, the CYP2C19 poor metabolizer was significantly associated with higher risk of major adverse cardiac and cerebrovascular events in patients with AMI (hazard ratio, 2.88; 95% confidence interval, 1.27-6.53; P=0.011). However, this finding was not seen in patients with stable angina. A significant interaction between CYP2C19 genotypes and disease subsets of AMI and stable angina was identified with respect to major adverse cardiac and cerebrovascular events (adjusted interaction P=0.045). The patients with AMI showed lower percent inhibition of P2Y12 compared with patients with stable angina in CYP2C19 poor metabolizer or CYP2C19 intermediate metabolizer genotype groups but not in CYP2C19 extensive metabolizer genotype group.
  
  
  CONCLUSIONS
  CYP2C19 poor metabolizer is associated with poor clinical outcome of clopidogrel therapy in Asian patients with AMI but not in those with stable angina possibly because of differential requirement of platelet suppression in patients with AMI and stable angina.
  
  
  BACKGROUND
  URL: clinicaltrials.gov. Identifier: NCTO1239914.
authors.affiliation: Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: Ho-Sook
authors.initials: HS
authors.lastname: Kim
authors.forename: Kiyuk
authors.initials: K
authors.lastname: Chang
authors.forename: Yoon-Seok
authors.initials: YS
authors.lastname: Koh
authors.forename: Mahn-Won
authors.initials: MW
authors.lastname: Park
authors.forename: Yun-Seok
authors.initials: YS
authors.lastname: Choi
authors.forename: Chul-Soo
authors.initials: CS
authors.lastname: Park
authors.forename: Minkyung
authors.initials: M
authors.lastname: Oh
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Kim
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Shon
authors.forename: Jae-Gook
authors.initials: JG
authors.lastname: Shin
authors.forename: Ki-Bae
authors.initials: KB
authors.lastname: Seung
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D060050:Angina, Stable / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D012307:Risk Factors; 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
keywords: CYP2C19 protein, human; acute myocardial infarction; angina, stable; clopidogrel; pharmacogenetics