title: CYP2C19 genotype has a greater effect on adverse cardiovascular outcomes following percutaneous coronary intervention and in Asian populations treated with clopidogrel: a meta-analysis.
abstract: BACKGROUND
  The degree to which cytochrome P450 (CYP) 2C19 genotype influences the effectiveness of clopidogrel remains uncertain because of considerable heterogeneity in results between studies and potential publication bias. Clopidogrel indication and ethnic population have been proposed to influence the effect of CYP2C19 genotype.
  
  
  RESULTS
  A systematic review was undertaken up to 14 November 2013. Meta-analysis of the CYP2C19 genotype effect was stratified by the predominant clopidogrel indication (percutaneous coronary intervention [PCI] versus non-PCI) and ethnic population (white versus Asian) of each primary study. The primary analysis was restricted to studies with ≥500 participants, which comprised 24 studies and a total of 36 076 participants. The association between carriage of ≥1 CYP2C19 loss-of-function (LoF) allele and major cardiovascular outcomes differed significantly (P<0.001) between studies of whites not undergoing PCI (relative risk 0.99 [95% confidence interval, 0.84-1.17]; n=7043), whites undergoing PCI (1.20 [1.10-1.31]; n=19,016), and Asians undergoing PCI (1.91 [1.61-2.27]; n=10,017). Similar differences were identified in secondary analyses of 2 CYP2C19 LoF alleles, stent thrombosis outcomes, and studies with ≥200 participants. Minimal heterogeneity was apparent between studies of Asian populations.
  
  
  CONCLUSIONS
  The reported association between CYP2C19 LoF allele carriage and major cardiovascular outcomes differs based on the ethnic population of the study and, to a lesser extent, the clopidogrel indication. This is potentially of major importance given that over 50% of Asians carry ≥1 CYP2C19 LoF alleles.
authors.affiliation: From the School of Medicine, Flinders University (M.J.S., A.R., R.A.M.); and School of Pharmacy and Medical Sciences, University of South Australia (M.D.W.), Adelaide, SA, Australia. michael.sorich@flinders.edu.au.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sorich
authors.affiliation: From the School of Medicine, Flinders University (M.J.S., A.R., R.A.M.); and School of Pharmacy and Medical Sciences, University of South Australia (M.D.W.), Adelaide, SA, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Rowland
authors.affiliation: From the School of Medicine, Flinders University (M.J.S., A.R., R.A.M.); and School of Pharmacy and Medical Sciences, University of South Australia (M.D.W.), Adelaide, SA, Australia.
authors.forename: Ross A
authors.initials: RA
authors.lastname: McKinnon
authors.affiliation: From the School of Medicine, Flinders University (M.J.S., A.R., R.A.M.); and School of Pharmacy and Medical Sciences, University of South Australia (M.D.W.), Adelaide, SA, Australia.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Wiese
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics*; D000077144:Clopidogrel; D054059:Coronary Occlusion / Q000188:drug therapy* / Q000235:genetics; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D016208:Databases, Factual; D005838:Genotype; D006801:Humans; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D012306:Risk; D015607:Stents; D013927:Thrombosis / Q000628:therapy; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine
keywords: CYP2C19; antiplatelet drug; meta-analysis; pharmacogenetics