课件：双重抗血小板治疗与消化道出血.ppt

SLIDE 28 The pharmacodynamic characteristics of a loading dose of clopidogrel were reported by Thebault et al. (in press). In one study, 10 healthy male volunteers received single-dose treatment with clopidogrel: 100 mg, 200 mg, 400 mg, or 600 mg, or placebo. ADP-induced platelet aggregation (5mm ADP) was assessed 2, 5 and 24 hours following treatment. This study indicated that maximal antiplatelet activity of clopidogrel occurs rapidly, within 2 hours of administration (at 200 mg to 600 mg). This level of platelet inhibition is similar to those observed at steady state after 3-7 days of 75 mg of clopidogrel once a day. Additional studies have determined that a loading dose of 300 mg to 400 mg is appropriate for initiating antiplatelet therapy with clopidogrel (Savcic et al. in press) , when rapid activity is necessary. Savcic M, Hauert J, Bachmann F et al. Clopidogrel loading dose regimens: kinetic profile of pharmacodynamic response in healthy subjects. Seminars in thrombosis and hemostasis. In press. Schuhlen H, Kastrati A, Dirschinger J et al. (1998a) Intracoronary stenting and risk for major adverse cardiac events during the first month? Circulation 98:104-111. Thebault JJ, Kieffer G, Cariou R. Single-dose pharmacodynamics of clopidogrel. Seminars in Thrombosis and Haemostasis 1999;25(Suppl 2): In press. Kleffer G et al (1989): Tolerance and pharmacological activity of a new antiplatelet agent clopidogrel (SR 25990C) in normal healthy volunteers after single increasing administrations. Thromb Haemost.:62(1);411. Abstract Draft 3 血小板表面有很多受体与血小板的激活有关，这些受体与相应的配体结合激活一系列的细胞内信号传导途径，并最终引起血小板表面的糖蛋白IIb/IIIa复合物的转化，使之能与纤维蛋白原结合，使临近的血小板发生聚集。抗血小板治疗就是阻断血小板聚集过程中的各个靶点。 多个权威指南明确了阿司匹林在心血管事件一级预防中的地位： 美国预防特别工作组（ U.S. PSTF ）指南： 10年冠心病风险大于等于6％的患者推荐长期使用阿司匹林75-160mg/d作为一级预防用药 美国心脏协会（AHA ）指南：10年冠心病风险大于等于10％的患者推荐长期使用阿司匹林75-160mg/d作为一级预防用药 美国胸科医师协会（ACCP）对于有中等冠脉事件风险的患者（10年风险大于等于10％）推荐使用阿司匹林75-160mg/d Victor L等将抗血小板药物分为六个组，分别为阿司匹林100mg组，阿司匹林100mg以上组、双嘧达莫组、氯吡格雷组、静脉和口服GP IIb/III