Assistance Publique Hôpitaux de Paris, Institut de Cardiologie, Pitié-Salpêtrière University Hospital, Paris, France.
J Am Coll Cardiol. 2010 Feb 23;55(8):815-22. doi: 10.1016/j.jacc.2009.08.082.
The purpose of this study was to determine whether the speed of response to clopidogrel loading predicts the final degree of response.
Fast inhibition of platelet aggregation is important in the setting of acute coronary syndromes and percutaneous coronary intervention, but its association with the final degree of inhibition is not well established.
We performed a post hoc analysis of the ALBION study; early kinetic profiles of adenosine diphosphate 20 micromol/l maximal platelet aggregation (MPA) and DeltaMPA (with baseline sample as reference) were studied at 8 time points within the 24 h after clopidogrel loading (300, 600, or 900 mg) in non-ST-segment elevation acute coronary syndrome patients. Low response was defined as DeltaMPA <10% over the first 24 h, fast response as DeltaMPA > or =10% at 1 h or before loading (the others being slow responders), and high post-treatment platelet reactivity as MPA > or =56.56% (fourth quartile). Inflammatory markers (PAC-1 and P-selectin) and vasodilator-stimulated phosphoprotein (VASP) were also evaluated according to onset of action.
Fifty-five percent of patients were slow responders. Noncurrent smoking and body mass index > or =25 kg/m(2) were associated with slower and lower responses. High post-treatment platelet reactivity was more frequent in slow responders (28% vs. 14%, p < 0.0001). There was a clopidogrel dose-effect relationship on DeltaMPA, with a trend toward faster onset of platelet inhibition in the 900-mg loading dose group. Slow responders had a slower and lower decrease in PAC-1 and P-selectin and higher VASP index at 6 h (76.5% vs. 66.4%, p = 0.019) and 24 h (70.3% vs. 61.5%, p = 0.049).
Slow response to clopidogrel, within the first hour of administration, is a reliable marker of low response at 24 h and high post-treatment platelet reactivity.
本研究旨在确定氯吡格雷负荷后反应速度是否可以预测最终反应程度。
急性冠脉综合征和经皮冠状动脉介入治疗时，血小板聚集的快速抑制非常重要，但它与最终抑制程度的关系尚未明确。
我们对 ALBION 研究进行了事后分析；在非 ST 段抬高型急性冠脉综合征患者中，于氯吡格雷负荷后 24 小时内的 8 个时间点（负荷剂量为 300、600 或 900mg 时），研究了腺苷二磷酸 20μmoll 最大血小板聚集（MPA）和 DeltaMPA（以基线样本为参照）的早期动力学特征。低反应定义为在最初 24 小时内 DeltaMPA<10%，1 小时内或负荷前反应速度>或=10%定义为快速反应（其余为慢反应），而治疗后血小板反应性高定义为 MPA>或=56.56%（第四四分位数）。还根据起效时间评估了炎症标志物（PAC-1 和 P-选择素）和血管扩张刺激磷蛋白（VASP）。
55%的患者为慢反应者。非吸烟和体质指数（BMI）>或=25kg/m2 与较慢和较低的反应相关。在慢反应者中，治疗后血小板反应性较高的情况更为常见（28%比 14%，p<0.0001）。DeltaMPA 与氯吡格雷剂量呈正相关，900mg 负荷剂量组血小板抑制作用的起效趋势更快。慢反应者的 PAC-1 和 P-选择素降低速度较慢、幅度较低，6 小时（76.5%比 66.4%，p=0.019）和 24 小时（70.3%比 61.5%，p=0.049）时 VASP 指数更高。
氯吡格雷负荷后 1 小时内的缓慢反应是 24 小时内低反应和治疗后血小板反应性高的可靠标志物。
