医学课件抗血小板治疗的个体化时代还有多远.ppt

* Tony In a study by Kim et al, individuals with 2 normal genes were considered homozygous extensive metabolizers of PLAVIX, those with 1 normal and 1 abnormal gene were heterozygous extensive metabolizers, and those with 2 abnormal genes were poor metabolizers. Poor metabolizers were found to have a significantly lower antiplatelet effect and heterozygous extensive metabolizers had reduced antiplatelet effect compared to extensive metabolizers. Therefore, polymorphic CYP2C19 genotypes appear to be major determinants of interindividual variability in PLAVIX responsiveness. Kim KA, Park PW, Hong SJ, Park J-Y. The effect of CYP2C19 polymorphisms on the pharmacokinetics and pharmacodynamics of clopidogrel: a possible mechanism for clopidogrel resistance. Nature. 2008;84:236-242. Genetic variation in metabolizing enzyme and transporter genes: comprehensive assessment in 3 major East Asian subpopulations with comparison to Caucasians and Africans. J Clin Pharmacol. 2010: published online before print February 19, 2010, doi: 10.1177/0091270009355161. Accessed June 16, 2010. Genetic polymorphism of cytochrome P450 2C19 in Mexican Americans: a cross-ethnic comparative study * Int J Cardiol. 2012 May 30 MADONNA Study 个体化抗血小板治疗可以减少PCI术后支架内血栓形成和ACS发生率 增加出血和死亡趋势但未到达显著统计学意义 TRILOGY ACS研究：更强的血小板抑制并未改善临床结局 Gurbel PA, et al. JAMA. 2012;308(17):1785-94. TRILOGY研究中9326例UA/NSTEMI患者随机接受氯吡格雷或普拉格雷治疗 2690例患者同意参与血小板功能亚组研究 因为无效PRU测量排除126例 血小板功能亚组研究 包含2564例患者 1286例接受普拉格雷 1278例接受氯吡格雷 一项随机、双盲、双模拟、阳性对照、事件驱动试验； 总研究纳入UA/NSTEMI事件发生10天内的非血运重建治疗患者9326例。其中27.5%参与血小板功能亚组研究； 通过VerifyNow P2Y12检测普拉格雷与氯吡格雷组的基线、随机化后2h及1,3,6,12,18,24,30月的血小板功能； 年龄75 岁及体重≥60kg者，给予普拉格雷10mgMD/氯吡格雷75mgMD；年龄75岁及体重60kg或年龄≥75岁者，给予普拉格雷5mgMD /氯吡格雷75mgMD 。 与氯吡格雷组比较，普拉格雷组各亚组人群血小板抑制均更强 Gurbel PA, et al. JAMA. 2012;308(17):1785-94. 30天中位PRU值 普拉 格雷 氯吡 格雷 P值 年龄75 岁及体重≥60kg 年龄75岁及体重60kg 年龄≥75岁 64 139 164 200 209 222 0.001 0.001 0.001 氯吡格雷组和普拉格雷组30个月CV死亡、MI或卒中发生率无显著差异 Gurbel PA, et al. JAMA. 2012;308(17):17