抗血小板药物疗效多样

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1、,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,抗血小板药物疗效多样性,北大医院 李建平,血小板功能的检测方法,LTA：透光率集合度金标准,流式细胞仪,PFA100 血小板功能检测仪,Ultegra快速血小板功能测定(RPFA-ASA),Cone and Plate(let)分析仪(CPA),阿司匹林抵抗的定义,氯吡格雷抵抗的定义,血小板对氯吡格雷反应呈正态发布,对氯吡格雷的反应有较大的个体差异，呈正态分布,该研究中,(,对含多种病人的数据库进行回顾性分析,),低反应病人,=4.2%,高反应病人,=4.8%,按低于或高于均数,2,标准差定义,Sereb

2、ruany V et al.,J Am Coll Cardiol,2005;45:246-51,60,“抵抗率”=15%,“抵抗”,24,小时,20,10,0,患者,-30,(-30,-20,(-20,-10,(-10,0,(0,10,(10,20,(20,30,(30,40,(40,50,(50,60,60,“抵抗率”=,31%,“抵抗”,2,小时,“抵抗”,“抵抗率”,=83%,24,12,0,患者,聚集率(),-30,(-30,-20,(-20,-10,(-10,0,(0,10,(10,20,(20,30,(30,40,(40,50,(50,60,60,5,天,22,11,0,患者,-3

3、0,(-30,-20,(-20,-10,(-10,0,(0,10,(10,20,(20,30,(30,40,(40,50,(50,60,60,“抵抗”,“抵抗率”=31%,聚集率(),聚集率(),聚集率(),聚集率()=基线聚集率(%)治疗后聚集率(%)，聚集率 10 定义为”抵抗“,Gurbel PA et al.Circulation.2003;107:2908-2913.,近25%的AMI患者对氯吡格雷反应异常,Matetzky S,et al.,Circulation,.2004;109(25):31713175.,血小板对阿司匹林反应多样性,Gum PA,Kottke-Marchan

4、t K,Poggio ED,et al.Profile and prevalence,of aspirin resistance in patients with cardiovascular disease.Am J,Cardiol.2001;88(3):230235.,Am J Cardiol.2001;88(3):230235.,近50%的阿司匹林抵抗的患者同时存在氯吡格雷抵抗,J Am Coll Cardiol,.2006;47(1):2733.,血小板集聚功能的改变（,5M ADP诱导的血小板聚集,）,血小板反应多样性在临床上意味着什么？,=-20,-10,0,11,20,31,40

5、,51,60,71,80,91,100,病例数,Adapted from:Serebrauny V et al.,J Am Coll Cardiol,2005;45:246-51,低反应者是否有发生血栓事件的危险,?,高反应者是否有出血的风险,?,氯吡格雷低反应者与再发血栓事件有关,Matetzky S et al.,Circulation,2004;109:3171-5,在AMI病人中，氯吡格雷抵抗增加再发血栓形成事件的危险性,1,st,N=15,2,nd,N=15,3,rd,N=15,4,th,N=15,Quartiles,C.6月CVS 事件发生率,%Points,1,st,N=15,2

6、,nd,N=15,3,rd,N=15,4,th,N=15,4,分位,B.血小板聚集下降的程度,1,2,3,4,5,6,Days,Clopidogrel Resistance,1,st,Q,2,nd,Q,3,rd,Q,4,th,Q,A.,ADP-介导的血小板聚集,病人按氯吡格雷治疗后的血小板抑制程度划分为4组,.,比较4组病人的,(a),与基线比较ADP介导的血小板集聚的变化l率,;(b),第6天与基线比较，血小板集聚率下降的程度;,(c),随访6月的主要心血管不良事件发生率,.,%of Baseline,P,=0.007,P,=70,24小时时,血小板聚集率(5mM ADP诱导的血小板聚集),

7、患者(%),300 mg 氯吡格雷,600 mg 氯吡格雷,Gurbel PA et al.J Am Coll Cardiol 2005;45 1382,(n=194),ALBION:较大剂量的氯吡格雷可以增加血小板抑制率,氯吡格雷剂量,CLEAR PLATELETS,：,600 mg,氯吡格雷比,300mg,可以更快更显著抑制血小板,Gurbel,P.A.et al.Circulation 2005;111:1153-1159,血小板功能监测调整氯吡格雷负荷剂量,Mean,SD,Control,VASP-guided,p,VASP after first LD,%,68 11,69 10,0

8、.4,VASP after adjustment,%,38 14*,*0.001,-Each additionnal bolus of 600 mg of clopidogrel decreased the number of patients with low response from 35 to 49%.,-Despite 2400 mg of clopidogrel 11(14%)patients remained low-responders.,血小板监测下的负荷剂量显著降低,PCI,后,MACE,MACE;n(%),Control,(n=84),VASP-guided,(n=78)

9、,Cardiovascular death,2(2),0,Stent thrombosis,4(5),0,Revascularization,2(2),0,Overall MACE,8(10)*,0,p=0.059,*,p=0.007,MACE:CV death,MI,revascularization,Log rank p=0.007,新型抗血小板药物Prasugrel,N Engl J Med,.,2007;357(20):20012015,.,新型抗血小板药物Prasugrel,stent thrombosis for all patients receiving at least on

10、e intracoronary stent,.,Lancet,.2008;371(9621):13531363,新型抗血小板药物ticagrelor,不需代谢为活性形式,半衰期 7,8小时,可逆性ADP受体拮抗剂,PLATO,研究设计,Primary endpoint:,CV death+,MI+Stroke,Primary safety endpint:,Total major bleeding,612-month exposure,Clopidogrel,If pre-treated,no additional loading dose;,if naive,standard 300 mg

11、loading dose,then 75 mg qd maintenance;,(additional 300 mg allowed pre PCI),Ticagrelor,180 mg loading dose,then,90 mg bid maintenance;,(additional 90 mg pre-PCI),NSTE-ACS(moderate-to-high risk)STEMI(if primary PCI),Clopidogrel-treated or-naive;,randomised within 24 hours of index event,(N=18,624),PC

12、I=percutaneous coronary intervention;ASA=acetylsalicylic acid;CV=cardiovascular;TIA=transient ischaemic attack,PLATO,主要终点,-KM,曲线,No.at risk,Clopidogrel,Ticagrelor,9,291,9,333,8,521,8,628,8,362,8,460,8,124,Days after randomisation,6,743,6,743,5,096,5,161,4,047,4,147,0,60,120,180,240,300,360,12,11,10,

13、9,8,7,6,5,4,3,2,1,0,13,Cumulative incidence(%),9.8,11.7,8,219,HR 0.84(95%CI 0.770.92),p=0.0003,Clopidogrel,Ticagrelor,K-M=Kaplan-Meier;HR=hazard ratio;CI=confidence interval,8,688,8,763,0,10,20,30,8,6,4,2,0,Cumulative incidence(%),Clopidogrel,Ticagrelor,4.77,5.43,HR 0.88(95%CI 0.771.00),p=0.045,No.a

14、t risk,Clopidogrel,Ticagrelor,9,291,9,333,8,875,8,942,8,763,8,827,Days after randomisation,31,90,150,210,270,330,8,6,4,2,0,Clopidogrel,Ticagrelor,5.28,6.60,8,688,8,673,8,286,8,397,6,379,6,480,Days after randomisation,*,HR 0.80(95%CI 0.700.91),p0.001,8,437,8,543,6,945,7,028,4,751,4,822,Cumulative incidence(%),PLATO,研究,-,主要终点,*Excludes patients with any primary event during the first 30 days,血小板功能监测,治疗高血压时监测血压吗？,治疗糖尿病时监测血糖吗？,使用华法令时监测INR吗？,使用抗血小板药物时，监测血小板功能吗？,谢 谢！,