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高白细胞计数和白细胞介素-10 可预测接受氯吡格雷治疗的患者的高治疗后血小板反应性。

High leukocyte count and interleukin-10 predict high on-treatment-platelet-reactivity in patients treated with clopidogrel.

机构信息

Cardiocenter, 3rd Internal-Cardiology Clinic, 3rd Medical School, Charles University and University Hospital Kralovske Vinohrady, Srobarova 50, Prague, Czech Republic.

出版信息

J Thromb Thrombolysis. 2012 May;33(4):349-54. doi: 10.1007/s11239-011-0659-5.

Abstract

According to recent trials, a significant number of patients do not have a completely effective response to clopidogrel. The aim of the study was to evaluate the rate of clopidogrel resistance in the context of important clinical characteristics and to specifically determine the relation between clopidogrel efficacy and biomarkers of inflammation. Consecutive non-selected patients following PCI were enrolled into the study. All patients received a loading dose of 600 mg of clopidogrel. The effect of clopidogrel was assessed using the VerifyNow assay 24 h after clopidogrel administration, clopidogrel resistance was defined as PRU ≥ 240. At the same time, standard parameters of biochemistry and hematology, the concentration of anti-inflammatory cytokine interleukin-10 and of soluble CD40 ligand, were measured. 378 patients were enrolled. 243 (64.3%) patients were responders (R) and 135 patients (35.7%) were non-responders (NR). Non-responders were older (R 65.7 ± 13.3, NR 69.8 ± 11.5, P < 0.05), had a higher prevalence of diabetes (R 26.3%, NR 38.5%, P < 0.05), were more often on mechanical ventilation (R 0.8%, NR 4.4%, P < 0.05). The leukocyte count (R 9.8 ± 3.5, NR 11.7 ± 12.8, P < 0.05), and concentration of IL-10 (R 3.1 pg/ml, NR 5.7 pg/ml, P < 0.05) was higher among non-responders. The concentration of CD40L was not significantly different between the groups. In a multivariate logistic regression, older age, higher weight, female gender, mechanical ventilation, and a higher concentration of leukocytes and IL-10 were associated with an increased risk for being a non-responder. Older, obese patients, especially women had a higher risk of high on-treatment-platelet-reactivity. Higher concentrations of leukocytes and interleukin-10 were also an important factor associated with the risk of low clopidogrel responsiveness.

摘要

根据最近的试验,相当数量的患者对氯吡格雷没有完全有效的反应。本研究的目的是评估在重要临床特征背景下氯吡格雷抵抗的发生率,并特别确定氯吡格雷疗效与炎症生物标志物之间的关系。连续入选接受 PCI 治疗的非选择性患者。所有患者接受氯吡格雷负荷剂量 600mg。在给予氯吡格雷后 24 小时使用 VerifyNow 检测评估氯吡格雷的效果,氯吡格雷抵抗定义为 PRU≥240。同时,测定标准的生化和血液学参数、抗炎细胞因子白细胞介素-10和可溶性 CD40 配体的浓度。共入选 378 例患者。243 例(64.3%)患者为反应者(R),135 例(35.7%)患者为无反应者(NR)。无反应者年龄较大(R 65.7±13.3,NR 69.8±11.5,P<0.05),糖尿病患病率较高(R 26.3%,NR 38.5%,P<0.05),更常接受机械通气(R 0.8%,NR 4.4%,P<0.05)。无反应者的白细胞计数(R 9.8±3.5,NR 11.7±12.8,P<0.05)和白细胞介素-10 浓度(R 3.1pg/ml,NR 5.7pg/ml,P<0.05)较高。两组间 CD40L 浓度无显著差异。多变量 logistic 回归分析显示,年龄较大、体重较高、女性、机械通气以及白细胞和白细胞介素-10 浓度较高与成为无反应者的风险增加相关。年龄较大、肥胖的患者,尤其是女性,发生高血小板反应的风险更高。白细胞和白细胞介素-10 浓度较高也是与低氯吡格雷反应性风险相关的重要因素。

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