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


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.
Department of Internal Medicine, Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Ryo
R
Nishio
Toshiro
T
Shinke
Hiromasa
H
Otake
Takahiro
T
Sawada
Yoko
Y
Haraguchi
Masakazu
M
Shinohara
Ryuji
R
Toh
Tatsuro
T
Ishida
Masayuki
M
Nakagawa
Ryoji
R
Nagoshi
Amane
A
Kozuki
Takumi
T
Inoue
Hirotoshi
H
Hariki
Tsuyoshi
T
Osue
Yu
Y
Taniguchi
Masamichi
M
Iwasaki
Noritoshi
N
Hiranuma
Akihide
A
Konishi
Hiroto
H
Kinutani
Junya
J
Shite
Ken-Ichi
K
Hirata
D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D044466:Asian People; D000077144:Clopidogrel; D017023:Coronary Angiography / Q000379:methods; D065731:Cytochrome P-450 CYP2C19; D054855:Drug-Eluting Stents; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011110:Polymorphism, Genetic; D013927:Thrombosis / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine