Paraoxonase-1 activity affects the clopidogrel response in CYP2C19 loss-of-function carriers

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• 作者：Ryo Nishio ; Toshiro Shinke ; Hiromasa Otake ; Masayuki Nakagawa ; Takumi Inoue ; Hirotoshi Hariki ; Tsuyoshi Osue ; Yu Taniguchi ; Masamichi Iwasaki ; Noritoshi Hiranuma ; Akihide Konishi ; Hiroto Kinutani ; Masaru Kuroda ; Ken-ichi Hirata
• 关键词：PON1 ; paraoxonase-1 ; DES ; drug-eluting stent ; CYP ; cytochromeP450 ; LOF ; loss-of-function ; OCT ; optical coherence tomography ; PRU ; platelet reactivity unit ; PCI ; percutaneous coronary intervention ; SES ; sirolimus-eluting stent ; PES ; paclitaxel-eluting sten
• 刊名：Thrombosis Research
• 出版年：2013
• 出版时间：November, 2013
• 年：2013
• 卷：132
• 期：5
• 页码：558-564
• 全文大小：652 K

文摘

Background

The impact of paraoxonase-1 (PON1) activity on the response to clopidogrel may differ in patients treated with drug-eluting stents (DES) in association with CYP2C19 loss-of-function (LOF) polymorphisms.

Methods

This study included 112 Japanese patients receiving clopidogrel (75 mg/day) and aspirin (100 mg/day) who underwent optical coherence tomography (OCT) examination 9 months after DES implantation. The CYP2C19 genotype was analyzed and LOF carriers (*1/*2, *1/*3, *2/*2, *3/*3, *2/*3) were identified. At the 9-month follow-up, platelet reactivity was determined by measuring the P2Y12 reactivity unit (PRU) using a VerifyNow P2Y12 assay, PON1 activity was evaluated and intra-stent thrombus was evaluated by OCT.

Results

Of the 112 Japanese patients, 75 were LOF carriers (67.0 % ). The patients were divided into tertiles according to the PON1 activity (tertile 1; < 230 U/L, tertile 2; 230-283 U/L, tertile 3; > 283 U/L). In the VerifyNowP2Y12 analysis, tertile 1 had a higher PRU than tertiles 2 and 3 in LOF carriers, and there was no difference among tertiles in non-carriers. The highest incidence of intra-stent thrombus was observed in tertile 1 followed by tertiles 2 and 3 in LOF carriers, whereas there was no such difference in non-carriers. Multivariate analysis revealed that LOF carriers and PON1 activity tertile 1 were independent predictors of intra-stent thrombus in all patients. In LOF carriers, tertile 1 was the only independent predictor for intra-stent thrombus.

Conclusion

Low PON1 activity is associated with a low response to clopidogrel and a high frequency of intra-stent thrombus only in LOF carriers.