Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.
J Thromb Thrombolysis. 2012 Nov;34(4):429-36. doi: 10.1007/s11239-012-0762-2.
Clopidogrel is a prodrug that undergoes bioconversion via cytochrome P450 system to form an active metabolite (AM) that binds to the platelet ADP receptor. The antiplatelet effect of clopidogrel is commonly assessed by measuring the aggregatory response to 5 μM ADP by light transmission aggregation (LTA) or multiple electrode aggregometry (MEA) or by the vasodilator-stimulated phosphoprotein platelet reactivity index (VASP-PRI). To determine which of these three tests of platelet ADP receptor pathway inhibition most closely correlates with clopidogrel AM levels. We analyzed blood samples from 82 patients with coronary artery disease who were randomized to receive double-dose or standard dose clopidogrel for 2 weeks. We measured peak clopidogrel AM levels, platelet aggregation in response to ADP and VASP-PRI on days 1, and repeated all the measures on days 7 and 14. Linear regression analysis was used to examine the correlation between clopidogrel AM and LTA, MEA and VASP-PRI. Bland-Altman plots were used to explore the agreement between tests of the antiplatelet effects of clopidogrel. Clopidogrel AM on day 1 correlated most closely with VASP-PRI (r = -0.5767) and demonstrated weaker correlations with LTA (r = -0.4656) and MEA (r = -0.3384) (all p < 0.01). Intra-class correlation (ICC) between VASP-PRI and LTA was 0.6446; VASP-PRI and MEA was 0.4720; and LTA and MEA was 0.4693. Similar results were obtained on days 7 and 14. Commonly used pharmacodynamic measures of clopidogrel response are only moderately correlated with clopidogrel AM levels and may not be suitable to measure the adequacy of clopidogrel therapy.
氯吡格雷是一种前体药物，通过细胞色素 P450 系统进行生物转化，形成与血小板 ADP 受体结合的活性代谢物 (AM)。氯吡格雷的抗血小板作用通常通过测量 5μM ADP 对光传输聚集 (LTA) 或多电极聚集 (MEA) 的聚集反应或通过血管扩张刺激磷酸蛋白血小板反应性指数 (VASP-PRI) 来评估。为了确定这三种血小板 ADP 受体途径抑制试验中哪一种与氯吡格雷 AM 水平最密切相关。我们分析了 82 例接受冠状动脉疾病治疗的患者的血液样本，这些患者被随机分为接受双倍剂量或标准剂量氯吡格雷治疗 2 周。我们在第 1 天测量氯吡格雷 AM 的峰值水平、ADP 诱导的血小板聚集和 VASP-PRI，并在第 7 天和第 14 天重复所有测量。线性回归分析用于检查氯吡格雷 AM 与 LTA、MEA 和 VASP-PRI 之间的相关性。Bland-Altman 图用于探索氯吡格雷抗血小板作用的测试之间的一致性。第 1 天的氯吡格雷 AM 与 VASP-PRI 相关性最强（r = -0.5767），与 LTA（r = -0.4656）和 MEA（r = -0.3384）的相关性较弱（均 p < 0.01）。VASP-PRI 和 LTA 之间的组内相关系数 (ICC) 为 0.6446；VASP-PRI 和 MEA 为 0.4720；LTA 和 MEA 为 0.4693。在第 7 天和第 14 天也得到了类似的结果。氯吡格雷反应的常用药效学测量与氯吡格雷 AM 水平仅中度相关，可能不适合测量氯吡格雷治疗的充分性。
