title: Impact of esomeprazole on platelet reactivity and clinical outcome according to CYP2C19 genotype in coronary heart disease patients during dual antiplatelet therapy.
abstract: OBJECTIVE
  The aim of this study was to investigate the effect of CYP2C19 polymorphism and co-therapy with esomeprazole on the antiplatelet efficacy of clopidogrel.
  
  
  BACKGROUND
  The antiplatelet efficacy of clopidogrel depends on CYP2C19 polymorphism or the co-administration of some kind of proton pump inhibitor (PPI).
  
  
  METHODS
  CYP2C19 genotype and the residual platelet reactivity (RPR) were measured in 361 coronary heart disease patients (male, mean age 69yrs), and the risk of cardiovascular events over a 3-month follow-up was assessed to evaluate the impact of co-administration of esomeprazole during dual antiplatelet therapy with aspirin and clopidogrel.
  
  
  RESULTS
  The values of RPR did not differ between esomeprazole and non-esomeprazole groups (4389 ± 1112 versus 4079 ± 1355 AU·min, P=0.103). RPR value was higher in intermediate metabolizers (IM) than in extensive metabolizers (EM) (4089 ± 1252 versus 3697 ± 1215 AU·min P=0.012) and, similarly, higher in poor metabolizers (PM) than in IM (4884 ± 1027 versus 4089 ± 1252 AU·min, P<0.001). There were no differences in RPR between esomeprazole and non-esomeprazole groups according to CYP2C19 genotype (EM, 3954 ± 1192 versus 3645 ± 1220 AU·min, P=0.361; IM, 4401 ± 1063 versus 4051 ± 1271 AU·min, P=0.293; PM, 4917 ± 669 versus 4876 ± 1099 AU·min, P=0.907, respectively). There was also no difference in clinical outcomes between esomeprazole and non-esomeprazole groups in the three-month follow-up (0% versus 0.92%, P=0.487).
  
  
  CONCLUSIONS
  These results suggest that concomitant use of esomeprazole with clopidogrel is not associated with reduced antiplatelet efficacy of clopidogrel or increased risk of cardiovascular events, irrespective of CYP2C19 genotype.
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: Noriaki
authors.initials: N
authors.lastname: Tabata
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.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Tsujita
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakamoto
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, and Center for Clinical Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Morita
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Medical and Pharmaceutical Sciences, and Center for Clinical Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kumagae
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Yamamoto
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Medical and Pharmaceutical Sciences, and Center for Clinical 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, and Center for Clinical 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: D000368:Aged; D001241:Aspirin / Q000008:administration & dosage; D001792:Blood Platelets / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000235:genetics; D000077144:Clopidogrel; D003327:Coronary Disease / Q000208:ethnology / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D064098:Esomeprazole / Q000008:administration & dosage / Q000627:therapeutic use*; D005006:Ethnicity; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D064098:Esomeprazole; D013988:Ticlopidine; D001241:Aspirin
keywords: Cardiovascular disease; Clopidogrel; Pharmacogenetics; Platelets; Polymorphism