Montalescot Gilles, Sideris Georges, Meuleman Catherine, Bal-dit-Sollier Claire, Lellouche Nicolas, Steg Ph Gabriel, Slama Michel, Milleron Olivier, Collet Jean-Philippe, Henry Patrick, Beygui Farzin, Drouet Ludovic
Institut de Cardiologie-Pitié-Salpêtriére University Hospital, Assistence Publique Hôpiteux de Paris (APHP), Paris, France.
J Am Coll Cardiol. 2006 Sep 5;48(5):931-8. doi: 10.1016/j.jacc.2006.04.090. Epub 2006 Aug 17.
We sought to compare the antiplatelet effects of three clopidogrel loading doses (LDs).
Administration of a 300-mg clopidogrel LD is beneficial in situations requiring rapid platelet inhibition. Whether higher LDs can provide further benefits remains unknown.
Patients (n = 103) with non-ST-segment elevation acute coronary syndromes were randomized to receive a 300-mg, 600-mg, or 900-mg clopidogrel LD, given on top of other standard therapy (including acetylsalicylic acid). The main outcome measure was inhibition of adenosine diphosphate-induced inhibition of platelet aggregation (IPA); inhibition of platelet activation, inflammatory markers, troponin I release, and major adverse cardiac events also were evaluated; all measures were blindly evaluated.
Compared with the 300-mg LD, greater doses were associated with significantly greater platelet inhibition, with dose-effect relationships observed for onset of action, maximal plateau, 24-h areas under the curves of IPA, and rates of low IPA (<10% at 6 h), using 20 micromol/l major adverse cardiac events. A significant dose-response was also observed for the vasodilator-stimulated phosphoprotein index, a measure of P2Y(12) receptor inhibition. Similar but nonsignificant trends were observed for troponin release and major adverse cardiac events. Bleeding rates were similar in each group.
In low-to-moderate risk patients with non-ST-elevation acute coronary syndromes, clopidogrel LDs >300 mg provide a faster onset of action, a higher IPA plateau, and greater reductions in platelet activation during the first 24 h. A 900-mg LD may induce a greater antiplatelet effect than 600 mg, when compared with the standard 300-mg regimen. These findings require further clinical confirmation.
我们试图比较三种氯吡格雷负荷剂量（LDs）的抗血小板作用。
给予300mg氯吡格雷负荷剂量在需要快速抑制血小板的情况下是有益的。更高的负荷剂量是否能带来更多益处仍不清楚。
103例非ST段抬高急性冠脉综合征患者被随机分为接受300mg、600mg或900mg氯吡格雷负荷剂量，在其他标准治疗（包括阿司匹林）基础上给药。主要结局指标是二磷酸腺苷诱导的血小板聚集抑制（IPA）；还评估了血小板活化抑制、炎症标志物、肌钙蛋白I释放及主要不良心脏事件；所有指标均采用盲法评估。
与300mg负荷剂量相比，更高剂量与显著更强的血小板抑制相关，在起效时间、最大平台期、IPA曲线下24小时面积及低IPA发生率（6小时时<10%）方面观察到剂量效应关系，采用20微摩尔/升主要不良心脏事件。对于血管扩张剂刺激的磷蛋白指数（一种P2Y(12)受体抑制指标）也观察到显著的剂量反应。在肌钙蛋白释放和主要不良心脏事件方面观察到相似但不显著的趋势。各组出血率相似。
在低至中度风险的非ST段抬高急性冠脉综合征患者中，氯吡格雷负荷剂量>300mg可提供更快的起效时间、更高的IPA平台期，并在最初24小时内更大程度地降低血小板活化。与标准的300mg方案相比，900mg负荷剂量可能比600mg诱导更强的抗血小板作用。这些发现需要进一步的临床证实。
