Kobe University Graduate School of Medicine, Division of Cardiovascular Medicine, Department of Internal Medicine.
Thromb Res. 2013 Nov;132(5):558-64. doi: 10.1016/j.thromres.2013.09.008. Epub 2013 Sep 13.
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.
This study included 112 Japanese patients receiving clopidogrel (75 mg/day) and aspirin (100mg/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.
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; 230-283U/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.
Low PON1 activity is associated with a low response to clopidogrel and a high frequency of intra-stent thrombus only in LOF carriers.
对接受药物洗脱支架（DES）治疗的患者，PON1 活性对氯吡格雷反应的影响可能因 CYP2C19 失活（LOF）多态性而异。
本研究纳入 112 例日本患者，这些患者在 DES 植入 9 个月后接受光学相干断层扫描（OCT）检查，他们接受氯吡格雷（75mg/天）和阿司匹林（100mg/天）治疗。对 CYP2C19 基因型进行分析，鉴定出 LOF 携带者（1/2、1/3、2/2、3/3、2/3）。在 9 个月的随访中，通过使用 VerifyNow P2Y12 检测测定 P2Y12 反应单位（PRU）来测定血小板反应性，评估 PON1 活性，并通过 OCT 评估支架内血栓。
在 112 例日本患者中，有 75 例为 LOF 携带者（67.0%）。根据 PON1 活性将患者分为三分位（三分位 1：<230 U/L，三分位 2：230-283 U/L，三分位 3：>283 U/L）。在 VerifyNowP2Y12 分析中，LOF 携带者中三分位 1 的 PRU 高于三分位 2 和 3，而非携带者中三分位间无差异。LOF 携带者中，三分位 1 的支架内血栓发生率最高，其次是三分位 2 和 3，而非携带者中无此差异。多变量分析显示，所有患者中，LOF 携带者和 PON1 活性三分位 1 是支架内血栓的独立预测因子。在 LOF 携带者中，三分位 1 是支架内血栓的唯一独立预测因子。
低 PON1 活性与 LOF 携带者氯吡格雷反应低和支架内血栓发生率高相关，而非 LOF 携带者则无此相关性。
