与第一代药物洗脱支架植入后相比，细胞色素P450 2C19功能丧失多态性对依维莫司洗脱支架植入后支架内血栓形成及病变转归的影响。
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.
作者信息
Konishi Akihide, Shinke Toshiro, Otake Hiromasa, Nishio Ryo, Sawada Takahiro, Takaya Tomofumi, Nakagawa Masayuki, Osue Tsuyoshi, Taniguchi Yu, Iwasaki Masamichi, Kinutani Hiroto, Masaru Kuroda, Takahashi Hachidai, Terashita Daisuke, Shite Junya, Hirata Ken-ichi
机构信息
Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Japan.
Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Japan.
出版信息
Int J Cardiol. 2015 Jan 20;179:476-83. doi: 10.1016/j.ijcard.2014.11.068. Epub 2014 Nov 6.
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.
背景
药物洗脱支架（DES）植入后，细胞色素P450（CYP）2C19功能缺失多态性对氯吡格雷反应的影响尚不清楚。
方法
共纳入196例患者，这些患者在第一代DES植入后8个月（120个病变）和新一代依维莫司洗脱支架（EES）植入后8个月（127个病变）接受了光学相干断层扫描（OCT）。根据CYP2C19多态性将患者分为3组：广泛代谢者（EMs）、中间代谢者（IMs）和慢代谢者（PMs）。比较3组的OCT结果。通过VerifyNow血小板反应单位（PRU）评估对氯吡格雷的反应性。
结果
与EES植入相比，第一代DES植入后支架内血栓形成的发生率显著更高（分别为35%和13%；p=0.0001）。在第一代DES组中，EMs、IMs和PMs的支架内血栓形成发生率显著增加（分别为21%、36%和63%；p=0.007），而EES植入后3组之间无显著差异（分别为10%、13%和20%；p=0.55）。每个支架组的EMs、IMs和PMs的PRU均显著增加。在多变量分析中，尽管第一代DES植入后PMs形成血栓的风险是非PMs的3倍，但EES植入后两组之间血栓形成无显著差异。第一代DES和EES预测支架内血栓形成的最佳PRU临界值分别为234和256。
结论
CYP2C19功能缺失多态性与第一代DES植入后支架内血栓形成的发生率较高相关，而EES植入后这种影响减弱。
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