Weerakkody Govinda J, Jakubowski Joseph A, Brandt John T, Payne Christopher D, Naganuma Hideo, Winters Kenneth J
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
J Cardiovasc Pharmacol Ther. 2007 Sep;12(3):205-12. doi: 10.1177/1074248407304731.
Multiple studies report response variability to a 300-mg clopidogrel loading dose (LD). Pooled platelet aggregometry data compared responses (change in maximal platelet aggregation [DeltaMPA] or inhibition of platelet aggregation [IPA]) to clopidogrel 300-mg (n = 131) or prasugrel 60-mg (n = 109) LDs. Poor responder rates were determined using empiric criteria (IPA < 10% and DeltaMPA < 10% for 20 microM and 5 microM adenosine diphosphate [ADP]) and Bayesian model-based criteria (IPA < 20% and DeltaMPA < 15% for 20 microM ADP; IPA < 25% and DeltaMPA < 20% for 5 microM ADP). Prasugrel achieved greater DeltaMPA and IPA from 2 to 24 hours post-LD (P < .001). For 20 microM ADP, poor responder rates for clopidogrel ranged from 17% to 43%; no prasugrel poor responders were observed. Regardless of the criterion, prasugrel 60 mg achieved greater IPA and fewer poor responders than the clopidogrel 300-mg LD.
多项研究报告了对300毫克氯吡格雷负荷剂量(LD)的反应变异性。汇总的血小板聚集测定数据比较了对300毫克氯吡格雷(n = 131)或60毫克普拉格雷(n = 109)负荷剂量的反应(最大血小板聚集变化[DeltaMPA]或血小板聚集抑制[IPA])。使用经验标准(对于20微摩尔和5微摩尔二磷酸腺苷[ADP],IPA < 10%且DeltaMPA < 10%)和基于贝叶斯模型的标准(对于20微摩尔ADP,IPA < 20%且DeltaMPA < 15%;对于5微摩尔ADP,IPA < 25%且DeltaMPA < 20%)确定低反应者率。普拉格雷在负荷剂量后2至24小时实现了更大的DeltaMPA和IPA(P <.001)。对于20微摩尔ADP,氯吡格雷的低反应者率为17%至43%;未观察到普拉格雷低反应者。无论采用何种标准,60毫克普拉格雷比300毫克氯吡格雷负荷剂量实现了更大的IPA且低反应者更少。