title: 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.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Japan.
authors.forename: Akihide
authors.initials: A
authors.lastname: Konishi
authors.affiliation: Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Japan. Electronic address: shinke@med.kobe-u.ac.jp.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Shinke
authors.affiliation: Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Otake
authors.affiliation: Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Nishio
authors.affiliation: Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Sawada
authors.affiliation: Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Japan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Takaya
authors.affiliation: Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakagawa
authors.affiliation: Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Osue
authors.affiliation: Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Taniguchi
authors.affiliation: Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Iwasaki
authors.affiliation: Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Japan.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kinutani
authors.affiliation: Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Japan.
authors.forename: Kuroda
authors.initials: K
authors.lastname: Masaru
authors.affiliation: Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Japan.
authors.forename: Hachidai
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Terashita
authors.affiliation: Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Shite
authors.affiliation: Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Hirata
mesh_terms: D000368:Aged; D000077144:Clopidogrel; D017023:Coronary Angiography; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D054855:Drug-Eluting Stents; D000068338:Everolimus; D005260:Female; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism; D011110:Polymorphism, Genetic; D012307:Risk Factors; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013927:Thrombosis / Q000188:drug therapy / Q000235:genetics*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000378:metabolism; D041623:Tomography, Optical Coherence
chemical_list: D007166:Immunosuppressive Agents; D010975:Platelet Aggregation Inhibitors; D003577:Cytochrome P-450 Enzyme System; D000068338:Everolimus; D000077144:Clopidogrel; D013988:Ticlopidine; D020123:Sirolimus
keywords: CYP2C19; Everolimus eluting stent; Optical coherence tomography; Thrombi