Impact of Cytochrome P450 2C19*2 Polymorphism on Intra-Stent Thrombus After Drug-Eluting Stent Implantation in Japanese Patients Receiving Clopidogrel

Circ J. 2011;75(1):99-105. doi: 10.1253/circj.cj-10-0525. Epub 2010 Nov 16.

Abstract

Background: The cytochrome P450 (CYP) 2C19*2 polymorphism is associated with reduced responsiveness to clopidogrel and poor clinical outcome after stent implantation. Despite the high frequency of this polymorphism in Japanese patients, its contribution to cardiac events and stent thrombi after drug-eluting stent (DES) implantation is not clear in this population.

Methods and results: One hundred Japanese patients received clopidogrel and underwent follow-up optical coherence tomography (OCT) after DES implantation. The patients were divided into 2 groups: those with at least one CYP2C19*2 allele (*2 carriers) and non-carriers. The incidence of stent thrombosis and major adverse cardiac events (MACE; ie, death, myocardial infarction, and target vessel revascularization) was compared between the 2 groups. In addition, OCT was used to evaluate the incidence of intra-stent thrombus, defined as a mass protruding into the lumen with significant attenuation. Of the 100 patients, 42 were *2 carriers. No remarkable differences in the baseline characteristics were noted. Although MACE did not differ significantly between the 2 groups, a subclinical intra-stent thrombus was detected more frequently in *2 carriers than in non-carriers (52.3% vs. 15.5%, P=0.0002). Multivariate logistic regression analysis showed that the presence of the CYP2C19*2 polymorphism was the only independent predictive factor for intra-stent thrombus (P=0.00006).

Conclusions: From these results it is suggested that CYP2C19*2 polymorphism is associated with subclinical thrombus formation among Japanese patients receiving clopidogrel. (Circ J 2011; 75: 99-105).

MeSH terms

  • Aged
  • Angioplasty, Balloon, Coronary / adverse effects
  • Angioplasty, Balloon, Coronary / instrumentation*
  • Angioplasty, Balloon, Coronary / mortality
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Asian Continental Ancestry Group / genetics*
  • Cardiovascular Agents / administration & dosage
  • Chi-Square Distribution
  • Cineangiography
  • Clopidogrel
  • Cytochrome P-450 CYP2C19
  • Drug-Eluting Stents*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Japan
  • Logistic Models
  • Male
  • Middle Aged
  • Myocardial Infarction / enzymology
  • Myocardial Infarction / genetics
  • Paclitaxel / administration & dosage
  • Phenotype
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Polymorphism, Genetic*
  • Prosthesis Design
  • Risk Assessment
  • Risk Factors
  • Sirolimus / administration & dosage
  • Thrombosis / diagnosis
  • Thrombosis / enzymology
  • Thrombosis / genetics*
  • Thrombosis / mortality
  • Thrombosis / prevention & control
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Time Factors
  • Tomography, Optical Coherence
  • Treatment Outcome

Substances

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