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【JACC】吸烟增强氯吡格雷对血小板的抑制作用
abstract：
Objectives: The purpose of this study was to examine the effect of cigarette smoking on the platelet response to clopidogrel.
Background: Response variability to clopidogrel therapy has been demonstrated. Clopidogrel is metabolically activated by several hepatic cytochrome P450 (CYP) isoenzymes, including CYP1A2. Cigarette smoking induces CYP1A2 and may, therefore, enhance the conversion of clopidogrel to its active metabolite.
Methods: Among 259 consecutive patients undergoing elective coronary stenting; 120 were on chronic clopidogrel therapy and were not loaded; and 139 were clopidogrel naïve and were loaded with 600 mg. There were 104 current smokers (CS) and 155 nonsmokers (NS). The adenosine diphosphate (ADP)-stimulated platelet aggregation (PA) was assessed by conventional aggregometry. The ADP-stimulated total and active glycoprotein (GP) IIb/IIIa expression were assessed with flow cytometry. Low PA was defined as the lowest quartile of 5 µmol/l ADP-induced post-treatment PA.
Results: Current smokers on chronic clopidogrel therapy displayed significantly lower PA and ADP-stimulated active GP IIb/IIIa expression compared with NS (p 0.0008 for both). Similarly, CS treated with 600 mg of clopidogrel displayed greater platelet inhibition and lower active GP IIb/IIIa expression compared with NS (p 0.05). In a multivariate Cox regression analysis, current smoking was an independent predictor of low PA (p = 0.0001).
Conclusion: Clopidogrel therapy in CS is associated with increased platelet inhibition and lower aggregation as compared with NS. The mechanism of the smoking effect deserves further study and may be an important cause of response variability to clopidogrel therapy.
来源：
http://content.onlinejacc.org/cgi/content/abstract/52/7/531?etoc The Association of Cigarette Smoking With Enhanced Platelet Inhibition by Clopidogrel
吸烟与氯吡格雷抑制血小板作用增强的关系
abstract：
Objectives: The purpose of this study was to examine the effect of cigarette smoking on the platelet response to clopidogrel.
目标：本研究的目的是探讨吸烟对血小板对氯吡格雷反应的作用。
Background: Response variability to clopidogrel therapy has been demonstrated. Clopidogrel is metabolically activated by several hepatic cytochrome P450 (CYP) isoenzymes, including CYP1A2. Cigarette smoking induces CYP1A2 and may, therefore, enhance the conversion of clopidogrel to its active metabolite.
背景：已有研究显示氯吡格雷治疗反应的变异性。氯吡格雷通过肝脏细胞色素P450（CYP）酶——包括CYP1A2——代谢性激活。吸烟诱导CYP1A2而且可能因此增强氯吡格雷转化为其活性代谢产物。
Methods: Among 259 consecutive patients undergoing elective coronary stenting; 120 were on chronic clopidogrel therapy and were not loaded; and 139 were clopidogrel naïve and were loaded with 600 mg. There were 104 current smokers (CS) and 155 nonsmokers (NS). The adenosine diphosphate (ADP)-stimulated platelet aggregation (PA) was assessed by conventional aggregometry. The ADP-stimulated total and active glycoprotein (GP) IIb/IIIa expression were assessed with flow cytometry. Low PA was defined as the lowest quartile of 5 µmol/l ADP-induced post-treatment PA.
方法：在259例连续的接受选择性冠脉支架的患者中，120例患者长期接受氯吡格雷治疗，没有给予负荷剂量；139例患者首次接受氯吡格雷治疗，给予600mg负荷剂量。104例患者为现时吸烟者(CS)，155例患者为非吸烟者（NS）。采用传统集合度测定评价ADP诱导的血小板聚集。采用流式计量术测量ADP激活的总的和活化糖蛋白（GP）IIb/IIIa表达。低血小板聚集定义为5µmol/l ADP诱导的血小板聚集在最低4分位区间。
Results: Current smokers on chronic clopidogrel therapy displayed significantly lower PA and ADP-stimulated active GP IIb/IIIa expression compared with NS (p 0.0008 for both). Similarly, CS treated with 600 mg of clopidogrel displayed greater platelet inhibition and lower active GP IIb/IIIa expression compared with NS (p 0.05). In a multivariate Cox regression analysis, current smoking was an independent predictor of low PA (p = 0.0001).
结果：接受慢性氯吡格雷治疗的患者中，现时吸烟者的血小板聚集和ADP诱导的活化GP IIb/IIIa表达显著低于非吸烟者（P值均为0.0008）。相似的，与非吸烟者相比，600mg氯吡格雷对于现时吸烟者的血小板抑制更强，活化GP IIb/IIIa表达更低（P=0.05）。在多因素Cox回归分析中，现时吸烟者是低血小板聚集的独立预测因子（P=0.0001）。
Conclusion: Clopidogrel therapy in CS is associated with increased platelet inhibition and lower aggregation as compared with NS. The mechanism of the smoking effect deserves further study and may be an important cause of response variability to clopidogrel therapy.
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作者:admin@医学,生命科学 2011-06-17 18:08
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