title: Comparison of loading with maintenance dose of clopidogrel on platelet reactivity in Chinese with different CYP2C19 genotypes prior to percutaneous coronary intervention.
abstract: BACKGROUND
  Whether two clopidogrel pretreatment strategies prior to elective percutaneous coronary intervention (PCI): a 300 mg loading dose (LD) in clopidogrel naїve patients and a 75 mg maintenance dose (MD) once daily in patients on chronic clopidogrel therapy play the same role in the platelet inhibition in Chinese with different CYP2C19 genotypes remains unknown. We aim to evaluate the impact on platelet inhibition by clopidogrel pretreatment strategy and its interaction effect with CYP2C19 genotype.
  
  
  METHODS
  Chinese patients undergoing PCI (n = 840) were assigned to 2×2 groups in the trial according to different clopidogrel pretreatment strategies (470 patients in LD, 370 patients in MD) and CYP2C19 genotypes (494 carriers of any CYP2C19 *2 or *3 loss-of-function allele, 346 non-carriers). The primary outcome was platelet aggregation (PA) as measured by the 10 µmol/L adenosine diphosphate induced light transmission aggregation.
  
  
  RESULTS
  Compared with MD group, LD strategy showed a significantly higher PA-((59.22 ± 11.67)% vs. (52.83 ± 12.17)%, P < 0.01), similar PA difference was observed in CYP2C19 loss-of-function carriers compared with non-carriers ((59.41 ± 10.91)% vs. (52.10 ± 12.90)%, P < 0.01). LD patients in either the CYP2C19 loss-of-function allele carrier or non-carrier group showed a significantly higher PA compared with MD group ((61.50 ± 10.61)% vs. (56.84 ± 10.74)%, P < 0.01; (56.06 ± 12.34)% vs. (46.88 ± 11.78)%, P < 0.01, respectively). A quantitative interaction effect was observed between clopidogrel pretreatment strategy and CYP2C19 genotype (P = 0.001).
  
  
  CONCLUSIONS
  The 300 mg LD strategy results in a decreased effect on platelet inhibition compared with the 75 mg MD in Chinese patients receiving clopidogrel prior to PCI, especially in the CYP2C19 2 or 3 loss-of-function allele non-carriers. (ClinicalTrials.gov number NCT01710436)
authors.affiliation: Key Laboratory of Clinical Trial Research in Cardiovascular Drugs, Ministry of Health, State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Centre for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Clinical Trial Research in Cardiovascular Drugs, Ministry of Health, State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Centre for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Lirong
authors.initials: L
authors.lastname: Yan
authors.affiliation: Key Laboratory of Clinical Trial Research in Cardiovascular Drugs, Ministry of Health, State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Centre for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Dongxue
authors.initials: D
authors.lastname: Wang
authors.affiliation: Key Laboratory of Clinical Trial Research in Cardiovascular Drugs, Ministry of Health, State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Centre for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Clinical Trial Research in Cardiovascular Drugs, Ministry of Health, State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Centre for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Han
authors.affiliation: Key Laboratory of Clinical Trial Research in Cardiovascular Drugs, Ministry of Health, State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Centre for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Tian
authors.affiliation: Key Laboratory of Clinical Trial Research in Cardiovascular Drugs, Ministry of Health, State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Centre for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Key Laboratory of Clinical Trial Research in Cardiovascular Drugs, Ministry of Health, State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Centre for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China. Email: liyishi@public3.bta.net.cn.
authors.forename: Yishi
authors.initials: Y
authors.lastname: Li
mesh_terms: D000368:Aged; D001792:Blood Platelets / Q000187:drug effects; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000601:surgery*; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000379:methods*; D010974:Platelet Aggregation / Q000187:drug effects; D011446:Prospective Studies; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine