PMID- 21627593
OWN - NLM
STAT- MEDLINE
DCOM- 20110714
LR  - 20181201
IS  - 0022-9040 (Print)
IS  - 0022-9040 (Linking)
VI  - 51
IP  - 2
DP  - 2011
TI  - [Factors determining clinical effectiveness of clopidogrel and prognosis of 
      patients with stable ischemic heart disease].
PG  - 8-18
AB  - 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).
FAU - Komarov, A L
AU  - Komarov AL
FAU - Panchenko, E P
AU  - Panchenko EP
FAU - Donnikov, A E
AU  - Donnikov AE
FAU - Shakhmatova, O O
AU  - Shakhmatova OO
FAU - Dzhalilova, G V
AU  - Dzhalilova GV
FAU - Iliushchenko, T A
AU  - Iliushchenko TA
LA  - rus
PT  - Comparative Study
PT  - Journal Article
PL  - Russia (Federation)
TA  - Kardiologiia
JT  - Kardiologiia
JID - 0376351
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 9007-49-2 (DNA)
RN  - A74586SNO7 (Clopidogrel)
RN  - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
RN  - EC 1.14.14.1 (CYP2C19 protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2C19)
RN  - OM90ZUW7M1 (Ticlopidine)
SB  - IM
MH  - Alleles
MH  - Aryl Hydrocarbon Hydroxylases/*genetics/metabolism
MH  - Clopidogrel
MH  - Cytochrome P-450 CYP2C19
MH  - DNA/*genetics
MH  - Female
MH  - Follow-Up Studies
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Liver/metabolism
MH  - Male
MH  - Middle Aged
MH  - Myocardial Ischemia/*drug therapy/genetics/metabolism
MH  - Platelet Aggregation Inhibitors/administration & dosage/pharmacokinetics
MH  - *Polymorphism, Genetic
MH  - Ticlopidine/administration & dosage/*analogs & derivatives/pharmacokinetics
MH  - Treatment Outcome
EDAT- 2011/06/02 06:00
MHDA- 2011/07/16 06:00
CRDT- 2011/06/02 06:00
PHST- 2011/06/02 06:00 [entrez]
PHST- 2011/06/02 06:00 [pubmed]
PHST- 2011/07/16 06:00 [medline]
PST - ppublish
SO  - Kardiologiia. 2011;51(2):8-18.