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1、急性冠脉综合征的抗栓治疗策略,北京安贞医院 周玉杰,急性冠状动脉综合征定义 (Acute Coronary Syndrome, ACS),冠状动脉粥样硬化斑块破裂(rupture)或糜烂(erosion)，继发完全或不完全闭塞性血栓形成为病理基础的一组临床综合征 根据心电图表现分为ST段抬高型（STE-ACS）和非ST段抬高型（NSTE-ACS）,ACS的分类,急性冠脉综合征 动脉粥样硬化疾病的“冰山一角”,CVD: An increasing problem,16.6 million people die every year from cardiovascular disease1 CVD
2、 1/3 of global deaths By 2010, leading cause of death in developing countries By 2020, 25 million deaths worldwide,1WHOwww.who.int/whosis/,急性冠状动脉综合征的流行病学,据流调资料显示我国急性冠脉综合征的年发病率为50/100,000人，而且这一数字正在逐年增加,N Engl J Med 2005;353:1124-34,在我国心脏疾病已超越恶性肿瘤成为首要死亡原因,我国冠心病年死亡率接近100/100,000人,N Engl J Med 2005;353:
3、1124-34,Vulnerable Plaque “ Active Volcano” Thrombotic effect ACS,Calcified Plaque “ Dormant Volcano ” Hemodynamic effect Stable Angina,Clinical Presentations of Coronary Disease,STE-MI和NSTE-ACS病理,Soft or Vulnerable Plaque Imaging by 64 slice MSCT,DRUG ELUTNG STENTS to eliminate the need for CABG op
4、erations ?,Dante Pazzanese,G,F,FIM Study: Vascular Healing 4-Year after SES Implantation (Pathological Findings),Courtesy of R. Virmani,Pt # 4 (Fast release),SEM showed 95% endothelized stent surface (F, G). Uncovered stent strut (F, arrow).,NSTE-ACS,NSTE-ACS,抗血小板治疗 阿司匹林 环氧化酶（COX-1）抑制剂 噻氯吡定类，包括氯吡格雷和
5、抵克力得 二磷酸腺苷（ADP）受体拮抗剂 糖蛋白（GP）IIb/IIIa受体拮抗剂，包括阿昔单抗、依替巴肽和替洛非班,抗血小板治疗的作用机制,JAMA. 2004;292:1875-1882,2004年ACCP7推荐的抗血小板治疗,JAMA. 2004;292:1875-1882,Aspirin History,First synthesized in pure form by Felix Hoffman of Friedr. Bayer & Co. in 1897.,(From the German acetylspirsaure + chemical suffix in),Aspirin
6、History,Due to problems with the original Aspirin powder being counterfeited, it became the first pharmaceutical agent ever sold in pill form in early 1900s. First pill in USA was 5 grains (325 mg).,阿司匹林,对于所有没有明确阿司匹林过敏的 NSTE ACS患者，推荐立即口服阿司匹林300mg，随后每日口服100mg 阿司匹林过敏或胃肠道疾患不能耐受的患者，应当使用氯吡格雷,Metabolic Pa
7、thways of Arachadonic Acid,Membrane Phospholipids,ARACHIDONIC ACID,Prostaglandin H2,COX-1,Thromboxane A2 Platelet Aggregation Vasoconstriction,Prostacyclin Platelet Aggregation Vasodilitation,Aspirin in the Treatment of ACS,Wallentin LC, et al. JACC 1991;18:1587-93.,0,3,6,9,12,Months,Probability of
8、Death or MI,Placebo,Aspirin 75 mg,Risk ratio 0.52 95% CL 0.37-0.72,What is “Aspirin Resistance?”,Inability of ASA to prevent treated patients from having thrombotic events.,Patrono C. J Thromb Haemost 2003;1:1710-3,Aspirin Resistant Patient Management,Eliminate interfering substances (ibuprofen) Inc
9、rease aspirin dose Use other anti-platelet medications such as clopidogrel to prevent recurrent ischemic events Educate patient on importance of compliance,Conclusions,ASA use associated with 23% reduction in the odds of vascular events ASA resistance 5-60% ASA resistance associated with increased r
10、isk of major adverse cardiovascular events,0,10,20,30,40,50,60,70,80,Q波心梗和死亡发生率的降低（%）,5,30,90,距离治疗开始的时间（天）,Lancet 1990;336:82730,ASA=75毫克 N=796,阿司匹林降低急性冠脉综合征患者心梗和死亡的发生,氯吡格雷,对于所有没有明确阿司匹林过敏的 NSTE ACS患者，推荐立即口服氯吡格雷300 mg，随后75 mg/日 对于不能马上进行诊断性导管术或冠脉造影后不能在5天内行CABG术的NSTE-ACS患者，推荐立即口服氯吡格雷300 mg，随后每日75 mg至9到
11、12个月，同时合用阿司匹林 对于正在服用氯吡格雷并准备接受CABG手术的患者，推荐术前日停用氯吡格雷,抵克力得,抵克力得由于其粒细胞减少等并发症多，临床上已渐被氯吡格雷所替代 抵克力得的适应症与氯吡格雷大致相同，首剂口服500mg，随后250mg每日次,GP b/a受体拮抗剂,对于中高危的NSTE-ACS患者，推荐早期应用依替巴肽或替洛非班，同时合用阿司匹林和普通肝素,GPIIb/IIIa受体拮抗剂临床研究,安慰剂较好,IIb/IIIa 较好,试验,安慰剂,IIb/IIIa,N,0.1,1,10,RESTORE,1.1%,0.9%,12,940,EPILOG,1.2%,0.9%,4891,RA
12、PPORT,1.3%,1.0%,5374,CAPTURE,1.3%,1.0%,6639,EPIC,1.7%,1.5%,2099,1.3%,IMPACT I,1.0%,6789,1.2%,IMPACT II,0.9%,10,799,ESPRIT,1.0%,0.8%,17,403,ISAR-2,1.1%,0.8%,17,804,ADMIRAL,1.2%,0.8%,18,104,EPISTENT,1.1%,0.8%,15,339,1.3%,CADILLAC,0.9%,20,186,OR & 95% CI,0.73 (0.55, 0.96) P=0.024,30 天死亡,27% P=0.024,GPI
13、Ib/IIIa受体拮抗剂在PCI中的应用,安慰剂更好,IIb/IIIa 拮抗剂更好,0,0.5,1,1.5,2,危险比 & 95% CI,试验名称,安慰剂,IIb/IIIa,N,EPIC,9.6%,6.6%,2,099,IMPACT-II,8.5%,7.0%,4,010,EPILOG,9.1%,4.0%,2,792,CAPTURE,9.0%,4.8%,1,265,6.3%,RESTORE,5.1%,2,141,10.2%,EPISTENT,5.2%,2,399,0.62 (0.55, 0.71) p 0.000000001,8.8%,汇总,5.6%,16,770,ESPRIT,2,064,10
14、.2%,6.3%,30 天死亡/心梗,38% (P 0.00000001),GPIIb/IIIa受体拮抗剂在PCI中的应用,GPIIb/IIIa受体拮抗剂在ACS中的应用,PRISM 7.1% 5.8%* 0.80 0.60-1.06 PRISM-PLUS 12.0% (*) 8.7% 0.70 0.50-0.98 ( ) 13.6%* 1.17 0.80-1.70 PARAGON-A 11.7% (l) 10.3% 0.87 0.58-1.29 (h) 12.3% 1.06 0.72-1.55 PURSUIT 15.7% (l) 13.4% 0.83 0.70-0.99 (h) 14.2%
15、0.89 0.79-1.00 PARAGON-B 11.4% 10.6% 0.92 0.77-1.09 GUSTO-IV 8.0% (24h) 8.2% 1.02 0.83-1.24 (48h) 9.1% 1.15 0.94-1.39 Overall 11.8% 10.8%t 0.91 0.85-0.98,O R,Placebo,IV Gp IIb/IIIa,95% CI,Placebo Better,Gp IIb/IIIa Better,0,1.0,2.0,Study,P=.015,* Without heparin. With/without heparin. (l), Low dose;
16、 (h), High-dose. Boersma E, et al. Lancet. 2002;359:189-198.,9% (P=0.015),30 天死亡/心梗,9%,替洛非班的用法,起始30分钟内，静脉输注0.4g/kg/min，随后0.1g/kg/min维持至少48小时；应与肝素联用，维持APTT在正常的1.5-2.0倍或ACT在200-250秒；或与低分子肝素联用 严重肾功能不全（血清肌酐清除率30ml）的患者应用时剂量减少50%,替洛非班的不良反应和禁忌症,不良反应 出血和血小板减少 禁忌症 对替洛非班过敏者 活动性内出血患者 颅内出血史、颅内肿瘤、动静脉畸形及动脉瘤患者 曾应用替洛非班造成血小板减少的患者,NSTE-ACS,抗凝治疗 普通肝素 低分子肝素 选择性间接抗Xa因子抑制剂：人工合成戊糖 凝血酶直接抑制剂（Direct thrombin inhibitors, DTI）,
