title: [Factors determining clinical effectiveness of clopidogrel and prognosis of patients with stable ischemic heart disease].
abstract: Aim of the study was to elucidate genetic and drug factors affecting efficacy of clopidogrel in patients with ischemic heart disease - inhabitants of central region of Russian Federation. We included 399 patients with IHD (79% men, mean age 58.3+/-9 years) receiving long term therapy with clopidogrel 75 mg/day (during stable manifestations of the disease) or 75-150 mg/day in combination with aspirin (in relation with recent elective percutaneous interventions). We studied carriage of polymorphisms of genes controlling intestinal absorption of clopidogrel (ABCB1 C3435T), activation of clopidogrel in the liver (CYP2C19 *1 *2), and also registered concomitant administration of proton pump inhibitors (PPI). Then we determined relationship of these factors to development of vascular complications (vascular death/myocardial infarction/requirement in revascularization) during 18 months followup. Among studied genetic factors carriage of allele variants CYP2C19 *1/*2 and *2/* (found in 25.5 and 1.8% of patients, respectively), possessed prognostic significance. In the group of clopidogrel monotherapy carriage of at least one *2 allele was associated with increased rate of vascular complications (33.3% vs. 11.3%) including thrombotic complications (27.7% vs. 3.2%; =0.01). In patients receiving 75 mg/day of clopidogrel in combination with aspirin total rate of thrombotic complications as well as of all adverse unfavorable outcomes was higher in *2 carriers compared with wild type homozygotes (14.0% vs.8.7% and 21.0% vs. 15.8%, respectively). In patients receiving double dose clopidogrel in combination with aspirin we found no worsening of outcomes associated with CYP2C19*2 carriage. In the multifactorial risk model independent predictors of vascular complications turned out to be CYP2C19 *2/*2 homozygosity (RR 4.9; =0.02) and concomitant PPI administration ( 1.8; p=0.05).
authors.forename: A L
authors.initials: AL
authors.lastname: Komarov
authors.forename: E P
authors.initials: EP
authors.lastname: Panchenko
authors.forename: A E
authors.initials: AE
authors.lastname: Donnikov
authors.forename: O O
authors.initials: OO
authors.lastname: Shakhmatova
authors.forename: G V
authors.initials: GV
authors.lastname: Dzhalilova
authors.forename: T A
authors.initials: TA
authors.lastname: Iliushchenko
mesh_terms: D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D004247:DNA / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D011110:Polymorphism, Genetic; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D004247:DNA; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine