title: The impact of gene polymorphism and high on-treatment platelet reactivity on clinical follow-up: outcomes in patients with acute coronary syndrome after drug-eluting stent implantation.
abstract: OBJECTIVE
  The current study sought to evaluate the clinical impact of newly reported genetic variations and their association with clopidogrel high on-treatment platelet reactivity (HTPR) in acute coronary syndrome (ACS) patients after drug-eluting stent (DES) implantation.
  
  
  RESULTS
  The study enrolled 1,016 consecutive patients with ACS undergoing DES implantation. A total of 19 tag single nucleotide polymorphisms (SNPs) were selected from CYP3A4/5, CYP2C19, P2Y12 and ABCB1 genes. ADP-induced light transmittance aggregometry (LTA) was performed to test the post-procedure maximum platelet agglutination (MPA). The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction (MI), stent thrombosis, and ischaemic stroke at one-year follow-up after DES placement. The secondary endpoint was the incidence of bleeding events. The post-procedure MPA was calculated and the cut-off point was determined for the HTPR. Using multivariate logistic regression analysis, the carriage of two CYP2C19 LOF alleles was an independent predictor of the post-procedure HTPR (OR: 2.8, 95% CI: 1.70-7.23, p<0.001). Through multivariate Cox regression analysis, the carriage of two CYP2C19 LOF alleles and the post-procedure HTPR were independent predictors of the primary endpoint (HR: 2.3, 95% CI: 1.40-4.97, p<0.001; HR: 2.9, 95% CI: 1.52-5.57, p<0.001, respectively). However, post-procedure MPA did not predict a bleeding event (HR: 0.9, 95% CI: 0.44-1.59, p=0.532).
  
  
  CONCLUSIONS
  In patients with ACS, the CYP2C19 LOF allele was associated with post-procedure HTPR and a subsequently increased risk of adverse clinical events at one-year follow-up following DES implantation and clopidogrel administration.
authors.affiliation: Department of Cardiology, Shenyang Northern Hospital, Shenyang, China.
authors.forename: Zhen-Yang
authors.initials: ZY
authors.lastname: Liang
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Han
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Cheng-Hui
authors.initials: CH
authors.lastname: Yan
authors.forename: Jian
authors.initials: J
authors.lastname: Kang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D054058:Acute Coronary Syndrome / Q000097:blood / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D002545:Brain Ischemia / Q000209:etiology / Q000401:mortality; D002681:China; D000077144:Clopidogrel; D003328:Coronary Thrombosis / Q000209:etiology / Q000401:mortality; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics*; D054855:Drug-Eluting Stents; D005260:Female; D005838:Genotype; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000209:etiology / Q000401:mortality; D016017:Odds Ratio; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects / Q000295:instrumentation* / Q000401:mortality; D010597:Pharmacogenetics; D010641:Phenotype; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D058925:Receptors, Purinergic P2Y12 / Q000187:drug effects / Q000235:genetics; D012307:Risk Factors; D020521:Stroke / Q000209:etiology / Q000401:mortality; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; C510164:CYP3A5 protein, human; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D013988:Ticlopidine