title: Clopidogrel High On-Treatment Platelet Reactivity in Patients with Carotid Artery Stenosis Undergoing Endarterectomy. A Pilot Study.
abstract: A considerable number of patients do not achieve an adequate response to clopidogrel. Our study aimed to evaluate genetic and non-genetic factors as possible risks for clopidogrel high on-treatment platelet reactivity (HTPR) in patients (n=112) with carotid artery stenosis undergoing endarterectomy (CEA).
  
  
  
  Using multiple-electrode impedance aggregometry (MEA) the antiplatelet effectiveness of clopidogrel was measured after 24 h, 7 and 30 days of clopidogrel treatment, which was introduced after elective CEA at a dose of 75 mg daily, for at least 30 days.
  
  
  
  HTPR was observed among 25% patients after clopidogrel therapy for 30 days. Further analysis showed that 53.3% of patients carrying the CYP2C19*2 gene variant had clopidogrel-HTPR, while in the wild type group there were 14.6% (p<0.001). Multivariate logistic regression analysis identified the CYP2C19*2 variant allele (OR 4.384; 95% CI 1.296-14.833, p=0.017) and high total cholesterol level (OR 2.090; 95% CI 1.263-3.459, p=0.004) as the only independent risk factors for clopidogrel-HTPR.
  
  
  
  The CYP2C19*2 gene variant and high total cholesterol level were major factors for clopidogrel- HTPR in patients with carotid artery stenosis undergoing CEA.
authors.affiliation: Faculty of Pharmacy, University of Belgrade, Serbia, Vojvode Stepe 450, 11000 Belgrade, Serbia.. dragana.backovicc@gmail.com.
authors.forename: Dragana
authors.initials: D
authors.lastname: Backovic
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ignjatovic
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Rakicevic
authors.forename: Mirjana
authors.initials: M
authors.lastname: Novkovic
authors.forename: Jelena
authors.initials: J
authors.lastname: Kusic-Tisma
authors.forename: Dragica
authors.initials: D
authors.lastname: Radojkovic
authors.forename: Evgenija
authors.initials: E
authors.lastname: Strugarevic
authors.forename: Branko
authors.initials: B
authors.lastname: Calija
authors.forename: Djordje
authors.initials: D
authors.lastname: Radak
authors.forename: Mirjana
authors.initials: M
authors.lastname: Kovac
mesh_terms: D000368:Aged; D016893:Carotid Stenosis / Q000097:blood / Q000175:diagnosis / Q000601:surgery*; D016009:Chi-Square Distribution; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D016894:Endarterectomy, Carotid / Q000009:adverse effects; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010597:Pharmacogenetics; D000071185:Pharmacogenomic Testing; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D010865:Pilot Projects; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011446:Prospective Studies; D012307:Risk Factors; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine