Impact of cytochrome P450 2C19 loss-of-function polymorphism on intra-stent thrombi and lesion outcome after everolimus-eluting stent implantation compared to that after first-generation drug-eluting stent implantation

Int J Cardiol. 2015 Jan 20:179:476-83. doi: 10.1016/j.ijcard.2014.11.068. Epub 2014 Nov 6.

Abstract

Background: The contribution of clopidogrel response due to cytochrome P450 (CYP) 2C19 loss-of-function polymorphism after drug-eluting stent (DES) implantation is unclear.

Methods: A total of 196 patients who had undergone optical coherence tomography (OCT) at 8 months following first-generation DES (120 lesions) and current-generation everolimus-eluting stent (EES) implantation (127 lesions) were enrolled. Patients were divided into 3 groups by CYP2C19 polymorphism: extensive metabolizers (EMs), intermediate metabolizers (IMs), and poor metabolizers (PMs). OCT findings were compared among the 3 groups. Responsiveness to clopidogrel was assessed by VerifyNow platelet reactivity unit (PRU).

Results: The incidence of intra-stent thrombi was significantly higher after first-generation DES implantation compared with EES implantation (35% vs 13%, respectively; p=0.0001). In the first-generation DES group, the incidence of intra-stent thrombi significantly increased among EMs, IMs, and PMs (21% vs 36% vs 63%, respectively; p=0.007), while there was no significant difference among the 3 groups after EES implantation (10% vs 13% vs 20%, respectively; p=0.55). The PRU significantly increased among EMs, IMs, and PMs in each stent group. In multivariate analyses, although PMs had a 3-fold higher risk of thrombi formation compared with non-PMs after first-generation DES implantation, there were no significant differences in thrombi formation between the 2 groups after EES implantation. The optimal PRU cutoff values for the prediction of intra-stent thrombi with first-generation DES and EES were 234 and 256, respectively.

Conclusion: CYP2C19 loss-of-function polymorphism is associated with a higher incidence of intra-stent thrombi after first-generation DES implantation, while the impact is attenuated following EES implantation.

Keywords: CYP2C19; Everolimus eluting stent; Optical coherence tomography; Thrombi.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Clopidogrel
  • Coronary Angiography
  • Cytochrome P-450 Enzyme System / genetics*
  • Drug-Eluting Stents*
  • Everolimus
  • Female
  • Genotype
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Male
  • Platelet Aggregation Inhibitors / metabolism
  • Polymorphism, Genetic
  • Risk Factors
  • Sirolimus / administration & dosage
  • Sirolimus / analogs & derivatives*
  • Thrombosis / drug therapy
  • Thrombosis / genetics*
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / metabolism
  • Tomography, Optical Coherence

Substances

  • Immunosuppressive Agents
  • Platelet Aggregation Inhibitors
  • Cytochrome P-450 Enzyme System
  • Everolimus
  • Clopidogrel
  • Ticlopidine
  • Sirolimus