抗血小板治疗的药学特点及临床应用解析-updatedApr.pptVIP

* 这是药代动力学/药效动力学研究结果，证明在血小板功能抵抗或CYP2C19慢代谢型患者，提高氯吡格雷治疗剂量（加倍量，与CURRENT研究剂量相似），可达到与正常代谢型患者相当的疗效。说明，加倍量氯吡格雷是克服血小板地反应性的一个有效方法。 * * * This slide depicts the balance of efficacy and safety observed in the trial. At the top is shown the significant reduction in the primary endpoint as presented a few moments ago. The number needed to treat to prevent one event was 46 At the bottom is the rate of TIMI major non CABG bleeds--a key safety endpoint-- which was 2.4% with prasugrel and 1.8% with clopidogrel—a 0.6% Absolute risk increase. The excess of 35 major bleeds with prasugrel corresponded to an HR of 1.32 and P value of 0.03 . The number of subjects who would need to be treated to result in one excess major bleed (NNH) was 167. * Non-CABG and CABG-related major bleeding The two treatment groups did not differ significantly in the rates of CABG-related PLATO or TIMI major bleeding. There was a higher rate of non-CABG related PLATO major bleeding (4.5% versus 3.8%, p=0.03) and non-CABG TIMI major bleeding (2.8% versus 2.2%, p=0.03) for ticagrelor as compared with clopidogrel. Reference Wallentin L, Becker RC, Budaj A, et al, for the PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. New Engl J Med. 2009;361:DOI:10.1056/NEJMoa0904327. * * * * * * * In fact, immediately after absorption, prasugrel is hydrolyzed by an intestinal carboxylase, hCE2, that rapidly converts about 90% of the parent drug to the intermediate metabolite R-95913 (from which the active clopidogrel metabolite R-138727 is formed) [19]. Therefore, more than half of the administered dose of prasugrel is rapidly activated [19]. A minor quantity of prasugrel is transformed into M1, which is the main urine metabolite excreted * 血小板受各种诱聚因子刺激，如血管内膜损伤后释放的炎症因子，激活血小板粘附聚集，形成血栓。抗血小板药物对血小板聚集的抑制作用，其速率应与新生血小板聚集作用处于动态平衡状态，这样才能维持一定的抗血小板聚集，同时保证不发生大出血。 * 当代抗血小板药物治疗的发展：缺血与出血风险的平衡 抗血小板药物单药治疗 双联抗血小板药物 更强的血小板聚集抑制剂 Reduction inIschemic Events Increase in Major Blee