acs 抗栓药物治疗最新进展

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,*,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,*,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,*,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,*,ACS,抗栓药物治疗最新进展,北京大学第一医院,霍勇,急性冠脉综合征（,ACS,）,不稳定型心绞痛,非,ST,段抬高型心肌梗死,ST,段抬高型心肌梗死,STEMI,NSTEMI,UA,目前的治疗方案,抗缺血药物,抗凝药物,普通肝素（,UFH,）,低分子肝素（,LMWH,）,抗血小板药物,阿司匹林,氯吡格雷,GPIIb/IIIa,受体拮抗剂,他汀类药物,血运重建,NSTE-ACS,的,趋势,及预后,Courtesy A Gitt,0,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,急性,STEMI/NSTEMI,后月数,STEMI vs.NSTEMI,后生存率,NSTEMI,STEMI,ST,段抬高,型心肌梗死（,STEMI,）,vs.,非ST,段抬高,型心肌梗死（,NSTEMI,）,1,年,累,计死亡率,一，抗凝药物,:,安全性新证据,出血患者,30,天事件发生率是未出血患者的,5,倍,Eikelboom Circulation 2006;114:774-782;published online August 14 2006,风险,5,倍,0,2,4,6,8,10,12,14,0,5,10,15,20,25,30,出血,未出血,累计,事件发生率,(%),33676,33419,33157,32990,32879,32769,32710,470,459,440,430,420,410,408,天,风险患者例数,未出血,出血,OASIS,注册、,OASIS-2,及,CURE,研究,:n=34146,不同抗凝药物的示意图,UFH,LMWH,磺达肝癸钠,高亲和力的戊糖结构,UFH-LMWH-,戊糖,(,磺达肝癸钠,),UFH,LMWH,安卓,(,磺达肝癸钠）,混和物,or,化合物,混和物,混和物,化合物,作用靶点,Xa,IIa,Xa,为主，,IIa,只作用于,Xa,蛋白结合,高,低,无,激活血小板,强,弱,无,磺达肝癸钠是人工合成的化合物，特异性抑制,Xa,因子，不与血浆蛋白结合，与血小板无相互作用。,因此磺达肝癸钠药代动力学更具有可预见性，抗凝作用更容易掌控。,磺达肝癸钠,2.5 mg.od up to 8 days,随机化,依诺肝素,1 mg/kg.bid for 2-8 days,1 mg/kg.od if ClCr30mL/min,2.OASIS 5 Investigators.N Engl J Med 1464-76,纳入统计分析,20,066(99.9%),第,9,天失访,:,磺达肝癸钠,:n=7,依诺肝素,:n=5,阿司匹林、氯吡格雷、,GP IIb/IIIa,抑制剂,根据当地实际情况制定导管,/PCI,计划,OASIS 5,研究：,41,个国家的多国、多中心随机双盲研究,20,078 UA/NSTEMI,患者,纳入统计分析,20,066 (99.9%),磺达肝癸钠,:5.8%(579,事件,),依诺肝素,:5.7%(573,事件,),第,9,天死亡,/,心肌梗塞,/RI,时间事件曲线,天,累积 风险,0.0,0.01,0.02,0.03,0.04,0.05,0.06,0,1,2,3,4,5,6,7,8,9,依诺肝素,磺达肝癸钠,HR:1.01,95%CI:0.90-1.13,p=0.007,非劣效,OASIS 5,研究,第,9,天疗效：磺达肝癸钠不劣于依诺肝素,(,主要终点,:,死亡,/,心肌梗塞,/RI),OASIS 5,研究,安卓显著降低,UA/NSTEMI,患者的大出血事件,OASIS 5 Investigators.N Engl J Med 2006;354:1464-76,时间（天）,累计风险,0,1,2,3,4,5,6,7,8,9,风险比,0.53,95%CI 0.45-0.62,依诺肝素,磺达肝癸钠,48%,与依诺肝素相比，安卓可减少第,9,天时的大出血事件达,48,OASIS 6,研究：,41,个国家的多国、多中心随机双盲研究,出院明确身体状况的患者,12,085,人,(99.9%),随访,:30,天,=12,072(99.8%),研究结束,=12,052(99.7%),溶栓剂,(SK,TPA,TNK,RPA),直接,PCI,或未实施再灌注,随机化,第一层,无普通肝素 使用指征,第二层,普通肝素使用指征,磺达肝癸钠,s.c.,2.5 mg od/8 days*,安慰剂,8,days*,普通肝素,i.v.,24-48 h,磺达肝癸钠,s.c.,2.5 mg od/8 days*,The OASIS-6 Trial Group.JAMA 2006;295:1519-30,12,092 STEMI,患者,磺达肝癸钠组30天内严重出血发生率更低,0,0.002,0.004,0.006,0.008,0.010,0.012,0.014,0.016,HR:0.79,(95%CI:0.58-1.09),p=0.15,累计风险,天,0,3,6,9,12,30,15,18,21,24,27,UFH,或安慰剂,磺达肝癸钠,磺达肝癸钠,:1.0%(61,起事件,),UFH,或安慰剂,:1.3%(79,起事件,),The OASIS-6 Trial Group.JAMA 2006;295:1519-30,天数,累积风险,0.0,0.02,0.04,0.06,0.08,0.10,0.12,0,3,6,9,12,15,18,21,24,27,30,UFH,磺达肝癸钠,HR=0.86(0.77-0.96),P=0.006,磺达肝癸钠显著降低STEMI患者的死亡率,The OASIS-6 Trial Group.JAMA 2006;295:1519-30,与常规治疗相比，安卓显著减少第,30,天的死亡,/,再梗塞,14,14%,中国专家共识治疗建议,ACS,患者选择,保守治疗,，建议优选磺达肝癸钠。,STEMI,患者未接受再灌注治疗，建议给予磺达肝癸钠。,对于,出血危险较高的患者,，应该首选磺达肝癸钠。,NSTACS,患者拟进行,早期介入治疗,，也可以选择磺达肝癸钠。,STEMI,患者如选择链激酶溶栓治疗，建议给予磺达肝癸钠辅助抗凝。,STEMI,患者如拟进行直接,PCI,，不建议选用磺达肝癸钠,患者如已经给予磺达肝癸钠，并拟行造影或,PCI,术，建议术中追加普通肝素，,50,100IU/kg,。,磺达肝癸钠不宜用于肌酐清除率,20ml/min,的患者。,选择性,Xa,因子抑制剂磺达肝癸钠急性冠脉综合征临床应用中国专家共识,二，抗血小板治疗：谁该强化？,2009ESC,最新公布：,25,087,例,ACS,患者,(UA/NSTEMI 70.8%,STEMI 29.2%),拟行早期,(24 h),介入治疗,拟行,PCI,缺血性,ECG,(80.8%),或心脏标记物,(42%),PCI 17,232,(70%),冠脉造影,24,769,(99%),非,PCI 7,855(30%),No Sig.CAD 3,616,CABG 1,809,CAD 2,430,随机化接受,(2 X 2,析因,):,氯吡格雷,:,剂量加倍,(600 mg,，继以,150 mg/d x 7d,，随后,75 mg/d)vs,标准剂量,(300 mg,继以,75 mg/d),ASA:,高剂量,(300-325 mg/d)vs,低剂量,(75-100 mg/d),有,效性结局,:30,天时,CV死,亡,MI 或,卒中,30,天时支架内血栓,安,全性结局,:出,血,(CURRENT 定,义的大,/,严重出血和,TIMI大,出血,),主,要亚组,:PCI v 非,PCI,最,初,7,天内氯吡格雷,(均,值,)7d 7 d 2 d 7d,99.8%的,患者完成随访,依从性,:,OASIS-7,波立维剂量加倍,(600mg/150mg*7,天,)vs,标准剂量,(300mg/75mg),的主要结局和各单一终点,标准剂量,剂量加倍,HR,95%CI,P,交互性,P,值,CV,死亡,/MI/,卒中,PCI(2N=17,232),4.5,3.9,0.85,0.74-0.99,0.036,0.016,非,PCI(2N=7855),4.2,4.9,1.17,0.95-1.44,0.14,总体,(2N=25,087),4.4,4.2,0.95,0.84-1.07,0.370,MI,PCI(2N=17,232),2.6,2.0,0.78,0.64-0.95,0.012,0.025,非,PCI(2N=7855),1.4,1.7,1.25,0.87-1.79,0.23,总体,(2N=25,087),2.2,1.9,0.86,0.73-1.03,0.097,CV,死亡,PCI(2N=17,232),1.9,1.9,0.96,0.77-1.19,0.68,1.0,非,PCI(2N=7855),2.8,2.7,0.96,0.74-1.26,0.77,总体,(2N=25,087),2.2,2.1,0.96,0.81-1.14,0.628,卒中,PCI(2N=17,232),0.4,0.4,0.88,0.55-1.41,0.59,0.50,非,PCI(2N=7855),0.8,0.9,1.11,0.68-1.82,0.67,总体,(2N=25,087),0.5,0.5,0.99,0.70-1.39,0.950,研究结论：,1,，波立维加倍对,PCI,患者有益，全部患者不得益。,2,，,ASA,加量未见任何得益,天,累积危险比,0,3,6,9,12,15,18,21,24,27,30,波立维标准剂量,氯吡格雷剂量加倍,42%,RRR,氯吡格雷剂量加倍,vs,标准剂量,确诊支架内血栓形成,(冠,脉造影证实,),氯吡格雷 剂量加倍,vs,标准剂量出血（总体人群）,氯吡格雷,标准剂量,N=12579,剂量加倍,N=12508,危险比,（,HR,）,95%CI,P,TIMI,大出血,1,0.95,1.04,1.09,0.85-1.40,0.50,CURRENT,大出血,2,2.0,2.5,1.25,1.05-1.47,0.01,CURRENT,严重出血,3,1.5,1.9,1.23,1.02-1.49,0.03,致死性,0.11,0.13,1.15,0.56-2.35,0.71,ICH,0.05,0.03,0.67,0.19-2.37,0.53,输注,RBC,2U,1.76,2.21,1.26,1.06-1.51,0.01,CABG,相关大出血,0.9,1.0,1.10,0.85-1.42,0.48,1,ICH,血红蛋白降低,5 g/dL(,每输注,1U,细胞计算为血红蛋白降低,1 g/dL),或致死性,2,严重出血,+,致残或眼底出血或需输血,2-3 U,3,致死性或血红蛋白,5 g/dL,明显的低血压,+,升压剂,/,手术,ICH,或输血,4 U,氯吡格雷 剂量加倍,vs,标准剂量出血（,PCI,人群）,氯吡格雷,标准剂量,N=8684,剂量加倍,N=8548,危险比,95%CI,P,TIMI,大出血,1,0.5,0.5,1.06,0.70-1.61,0.79,CURRENT,大出血,2,1.1,1.6,1.44,1.11-1.86,0.006,CURRENT,严重出血,3,0.8,1.1,1.39,1.02-1.90,0.034,致死性,0.15,0.07,0.47,0.18-1.23,0.125,ICH,0.035,0.046,1.35,0.30-6.04,0.69,RBC,输注,2U,0.91,1.35,1.49,1.11-1.98,0.007,CABG,相关 大出血,0.1,0.1