抗血小板药物疗效多样

,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,*,血小板功能的检测方法,LTA,：透光率集合度,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,Serebruany 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, -30,(-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-Marchant 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,-10,0,11,20,31,40,51,60,71,80,91,100,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,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,),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 10,0.4,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),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 one 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 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),PCI = 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,6,743,6,743,5,096,5,161,4,047,4,147,0,60,120,180,240,300,360,12,11,10,9,8,7,6,5,4,3,2,1,0,13,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. at 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！,