Effect of cytochrome P450 2C19 polymorphism on target lesion outcome after drug-eluting stent implantation in japanese patients receiving clopidogrel

Circ J. 2012;76(10):2348-55. doi: 10.1253/circj.cj-12-0476. Epub 2012 Jul 3.

Abstract

Background: Cytochrome P450 (CYP) 2C19 polymorphism is associated with reduced responsiveness to clopidogrel and poor clinical outcome after drug-eluting stent (DES) implantation, but its contribution to lesion outcome after DES implantation is unclear.

Methods and results: The study included 160 Japanese patients who received clopidogrel and underwent DES implantation with follow-up angiography. Patients were divided into 3 groups by CYP2C19 polymorphism: extensive metabolizers (EM), intermediate metabolizers (IM), and poor metabolizers (PM). The incidence of major adverse cardiac events (MACE) and target lesion revascularization (TLR) were compared among the 3 groups. Optical coherence tomography (OCT) was performed for 120 patients to evaluate the incidence of intra-stent thrombi. Of the 160 patients, the proportion of EM, IM, and PM was 37.5%, 48.1%, and 14.4%, respectively. The incidence of TLR and MACE was more frequent in IM and PM than EM (TLR: 18.2% and 26.1% vs. 3.3%, P=0.008, MACE: 22.1% and 30.4% vs. 5.0%, P=0.005). Among the 120 patients who underwent follow-up OCT, intra-stent thrombi were more frequently detected in IM and PM than in EM (45.6% and 63.2% vs. 20.5%, P=0.005). The incidence of TLR was significantly higher in patients with than in those without intra-stent thrombi (27.7% vs. 6.8%, P=0.003).

Conclusions: CYP2C19 loss-of-function polymorphism might be associated with the incidence of MACE and TLR in association with intra-stent thrombi.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Asian People
  • Clopidogrel
  • Coronary Angiography / methods
  • Cytochrome P-450 CYP2C19
  • Drug-Eluting Stents*
  • Female
  • Follow-Up Studies
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / pharmacokinetics
  • Polymorphism, Genetic*
  • Thrombosis* / drug therapy
  • Thrombosis* / enzymology
  • Thrombosis* / genetics
  • Thrombosis* / pathology
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacokinetics

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Ticlopidine