ACS抗栓治疗的平衡出血与止血.ppt

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,*,*,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,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,*,*,*,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,*,*,*,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,*,*,*,*,*,*,ACS,抗栓治疗的平衡：出血与止血,1,16-20%,12-15%,8-12%,6-10%,4-8%,Death/MI,bleeding,1988,ASA,1992,ASA+,Heparin,1998,ASA+,Heparin+,Anti-GPIIB/IIIA,2003,ASA+,LMWH+,Clopidogrel,+,Intervention,With permission from Christopher Cannon,1988,由于抗栓强度提高缺血事件渐低，但同时出血风险渐高,出血,止血,一个事物的两个方面,抗栓强度,事件,2,ACS,抗栓治疗的,有效性与安全性,ASA,的剂量,氯吡格雷的剂量,氯吡格雷的短期及长期应用结果,新型抗血小板药物,三联抗血小板药物,如何减少,ACS,患者的出血风险,出血并发症带来的风险,进行出血危险因素的评估,输血带来的风险,选择合适的穿刺部位、介入器械,减少消化道出血,3,ACS,抗栓治疗的,有效性与安全性,ASA,的剂量,氯吡格雷的剂量,氯吡格雷的短期及长期应用结果,新型抗血小板药物,三联抗血小板药物,如何减少,ACS,患者的出血风险,出血并发症带来的风险,进行出血危险因素的评估,输血带来的风险,选择合适的穿刺部位、介入器械,减少消化道出血,4,CURE:,增加,ASA,剂量并不增加抗栓效果,CV death,MI,stroke,refractory angina,Major bleeding,Aspirin dose,P0.99,Abciximab,Placebo,Kastrati A et al.,JAMA,2006;295:1531-38,24,临床疗效终点,（标准两联,+,西洛他唑）,Yaling,Han,et al.,Am Heart J.,2009;157(4):733-9,与双联抗血小板治疗相比，三联抗血小板治疗可以明显降低患者,1,年,MACCE,的发生,25,出血事件,（标准两联,+,西洛他唑）,Yaling,Han,et al.,Am Heart J.,2009;157(4):733-9,三联抗血小板治疗并未增加出血,26,ACS,抗栓治疗的,有效性与安全性,ASA,的剂量,氯吡格雷的剂量,氯吡格雷的短期及长期应用结果,新型抗血小板药物,三联抗血小板药物,如何减少,ACS,患者的出血风险,出血并发症带来的风险,进行出血危险因素的评估,输血带来的风险,选择合适的穿刺部位、介入器械,减少消化道出血,27,死亡,4.3%,心肌再梗死,2.5%,心力衰竭,8.0%,心源性休克,2.6%,中风,0.8%,出血,9.9%,Bhatt DL,et al.,JAMA,.,2004 Nov 3;292(17):2096-104.,CRUSADE,研究表明出血是,ACS,院内最严重并发症,28,Age,75 years,1.64(1.32-2.02),0.0001,Female gender,1.92(1.61-2.29),0.0001,Diabetes,1.20(1.00-1.44),0.06,Hypertension,1.24(1.01-1.52),0.05,No prior PCI,1.32(1.08-1.62),0.01,Anemia*,1.87(1.54-2.28),0.0001,Renal insufficiency,1.53(1.24-1.90),0.0001,Baseline ST-segment deviation,1mm,1.35(1.13-1.61),0.001,Baseline cardiac biomarker elevation,1.43(1.19-1.74),0.001,Heparin,+GPI vs.,Bivalirudin,1.95(1.56-2.44),0.0001,*Anemia was defined as baseline hemoglobin 13,g/dL,in men and 12,g/dL,in women,.,Renal insufficiency was defined as a,creatinine,clearance 60 ml/minute as calculated by the Cockcroft-,Gault,equation.,Unfractionated,heparin or,enoxaparin,.,Odds ratio 95%CI,ACS,患者出血的独立危险因素,P-value,OR(95%CI),Manoukian,SV,Feit,F,Mehran,R,et al.J Am,Coll,Cardiol,2007;49:1362-8.,ACS,患者的出血高危因素包括：高龄、女性、糖尿病、高血压、未接受过,PCI,治疗、贫血、肾功不全、,ST,段抬高大于,1mm,、心肌标志物升高等,29,ACS,抗栓治疗的,有效性与安全性,ASA,的剂量,氯吡格雷的剂量,氯吡格雷的短期及长期应用结果,新型抗血小板药物,三联抗血小板药物,如何减少,ACS,患者的出血风险,出血并发症带来的风险,进行出血危险因素的评估,输血带来的风险,选择合适的穿刺部位、介入器械,减少消化道出血,30,Moscucci M et al.,Eur,Heart J,2003;24:1815-23.,P0.001,Overall Unstable NSTEMI STEMI,ACS Angina,Patients(%),ACS,出血患者死亡率升高,24,045 ACS patients in the,GRACE registry,in-hospital death,31,26,452 patients from PURSUIT,PARAGON A,PARAGON B,GUSTO IIb NST,Bleeding severity and adjusted hazard of death,*,p0.0001,Bleeding Severity30d Death30d Death/MI6m Death,Mild*1.61.31.4,Moderate*2.73.32.1,Severe*10.65.67.5,*Bleeding as a time-dependent covariate,Rao SV,et al.,Am J,Cardiol,.2005 Nov 1;96(9):1200-6.,Epub,2005 Sep 12,ACS,出血越严重患者死亡风险越高,32,ACS,抗栓治疗的,有效性与安全性,ASA,的剂量,氯吡格雷的剂量,氯吡格雷的短期及长期应用结果,新型抗血小板药物,三联抗血小板药物,如何减少,ACS,患者的出血风险,出血并发症带来的风险,进行出血危险因素的评估,输血带来的风险,选择合适的穿刺部位、介入器械,减少消化道出血,33,30-Day Survival By Transfusion Group,Rao SV,et.al.,JAMA,2004;292:15551562.,输血增加,ACS,短期死亡率,N=24,111,34,Increased 1-year mortality in transfused patients,Adjusted Odds Ratio 4.26(2.258.08),输血增加,ACS,患者长期死亡率,:,REPLACE 2 One,-,Year Mortality,P0.0001,Manoukian SV,Voeltz MD,Attubato,MJ,Bittl,JA,Feit F,Lincoff AM.CRT 2005.Abstract.,35,输血增加,ACS-PCI,人群缺血事件发生率,P0.0001 for all,Manoukian SV,Voeltz MD,Feit F et al.,TCT,2006.,Results:The ACUITY Trial(N=13,819),36,ACS,抗栓治疗的,有效性与安全性,ASA,的剂量,氯吡格雷的剂量,氯吡格雷的短期及长期应用结果,新型抗血小板药物,三联抗血小板药物,如何减少,ACS,患者的出血风险,出血并发症带来的风险,进行出血危险因素的评估,输血带来的风险,选择合适的穿刺部位、介入器械,减少消化道出血,37,Vascular Closure Devices in PCI,Predictors of PCI Major Vascular Complications,(n=5667,94%of REPLACE-2),Variable,Odds Ratio,95%CI,P-value,Treatment group(H+GPI vs.BIV),2.38,1.61-3.82,0.0001,W/O Vascular closure device,(n=1400),1.85,1.18-2.90,0.007,Sheath dwell time(in hours),1.06,1.03-1.09,0.0001,GFR 60 ml/min/1.73 m,2,1.70,1.08-2.68,0.02,Female gender,2.30,1.53-3.46,0.0001,Fazel,R,Voeltz,MD,Feit,F,Attubato,MJ,Rab,ST,Samady,H,Rao,SV,Manoukian,SV.ACC 2007.Abstract.,Stepwise logistic regression.c-statistic 0.71.Test for goodness-of-fit indicated satisfactory fit.,肝素,+GPI,以及不用封堵器均可增加出血，动脉鞘留置时间与出血呈正相关。对这些因素进行干预、应用封堵器可减少出血,38,Sheath Size and Vascular Complications in PCI,Blankenship JC et al.Am J,Cardiol,1998;81:36-40.,鞘管的尺寸也与出血密切相关，应当尽量减少,39,Unadjusted and Adjusted Success and Complication Rates Between r-PCI and f-PCI,Rao,SV et al.JACC,Intv,2008;1:379-86.,r-PCI,（经桡动脉介入治疗）与,f-PCI,（经股动脉介入治疗）相比有相同的手术成功率，但可以明显减少出血的发生,40,ACS,抗栓治疗的,有效性与安全性,ASA,的剂量,氯吡格雷的剂量,氯吡格雷的短期及长期应用结果,新型抗血小板药物,三联抗血小板药物,如何减少,ACS,患者的出血风险,出血并发症带来的风险,进行出血危险因素的评估,输血带来的风险,选择合适的穿刺部位、介入器械,减少消化道出血,41,Clopidogrel,is a,prodrug,;requires conversion by the liver primarily via CYP3A4 and CYP2C19 to an active metabolite,PPIs,are strong inhibitors of CYP2C19 activity,Clopidogrel,and,PPIs,The OCLA study,PRI:Platelet Reactivity Index as measured by vasodilator stimulated,phosphoprotein,(VASP),Gilard,et al.J Am,Coll,Cardiol,2008;51:256-60.,p0.0001,42,Concomitant use of,clopidogrel,and PPI after hospital discharge for ACS was associated with an increased risk of adverse outcomes,PPI,与氯吡格雷合用影响,ACS,病人的预后,All,P,0.05,回顾性分析,03.1006.1,期间,127,家,VA,医院,8205,例,ACS,病人资料,(,最后随访时间,06.9.31),JAMA.2009;301(9):937-944,43,44,FDA,还是对此发出了通告（,2009.11.17,）,最新临床资料显示，如果同时服用氯吡咯雷和,PPI,，氯吡咯雷的疗效将减弱,若高危患者同时服用氯,吡,格雷和,PPI,，氯,吡,格雷可能无法达到最大抗血小板作用,新的药品说明书中生产厂家将增加最新临床研究的结果,45,Thank You,