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,Click to edit Master title style,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Proposals subject to consultation,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Confidential. Draft for discussion purposes. Subject to relevant consultation and legal requirements.,*Footnote,Source:Source,Unit of measure,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,STICKER,Legend,Legend,Legend,Legend,Legend,Legend,Legend,Legend,Legend,Legend,Legend,Legend,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Proposals subject to consultation,NSTE ACS,抗凝治疗策略,无锡人民医院 心脏中心,羊镇宇,NSTE ACS,治疗的重要环节,血运重建,抗缺血治疗,抗血小板治疗,抗凝治疗,长期管理,Eur,Heart J.2007,28:15981660,ESC,指南抗凝治疗推荐,所有,NSTE-ACS,患者均应接受抗凝治疗（,I-A,）,2011 ESC,AHA,指南,(,NSTE-ACS,抗凝相关,),患者接受抗血小板治疗的同时应接受抗凝治疗,抗凝药物的选择要兼顾疗效和安全性,新增拟行紧急侵入治疗患者的抗凝治疗建议,其他：,不推荐交叉应用普通肝素和,LMWH,内皮损伤诱发血栓形成示意图,凝血酶是血管损伤、凝血及血小板激活的纽带,胶原,组织,因子,凝血酶,IIa,血小板,激活,凝血酶原,II,ADP,TXA,2,凝血,瀑布,血栓,纤维蛋白原,纤维蛋白,血小板,聚集,凝血酶是凝血过程中的重要介质，可催化纤维蛋白及诱发血小板聚集,Pollack,CV,et al.,The Journal of Emergency Medicine,.,2008,(,34,),4,:,417,-,428,AMI,闭塞性血栓的构成以混合性血栓为主,91,例透壁心肌梗死患者的尸解资料,血小板血栓,15% (14,of 91),以血小板为主的混合血栓 5%,( 4,of 91),以纤维蛋白和红细胞为主的混合血栓 80% (73,of 91),K. Peter,Rentrop, MD Thrombi in Acute Coronary Syndromes Revisited and Revised,Circulation.,2000;101:1619.),Sinapius,D.,Zur,Morphologie,verschliessender,Koronarthromben,.,Dtsch,Med,Wochenschr,.,1972;97:544551.,这提示抗凝治疗与抗血小板治疗同等重要,UA/NQMI,患者，强化抗血小板治疗并不能改变凝血活跃的状态,For the,Clopidogrel,in Unstable angina to prevent Recurrent Events (CURE) Study,Investigators,European,Heart Journal,(2002) 23, 1771-779,Oldgren, J. et al.,Arterioscler,Thromb,Vasc,Biol,2001;21:1059-1064,Probability of death during long-term follow-up: median, 29 months; minimum, 12 months; and maximum, 50 months in relation to baseline (,pretreatment,) levels of the respective coagulation marker,凝血指标与远期预后的关系,死,亡,可,能,性,法国一项针对急性心肌梗塞患者,PCI,术前使用抗凝药物的研究,Francois,Schiele,et,al.Circulation,. 2009;120:S951-S952.,spo.escardio.org/eslides/view,-ESC2009,未抗凝组,&UFH,组,根据,ACT,调整,UFH,用量,.,患者使用,enoxaparin,8h,PCI,术中依诺肝素,0.3mg/kg,患者使用磺达肝癸钠,PCI,术中,UFH50U/kg,PCI,术前使用抗凝药物,STEMI,，,NSTMI,两类患者均有获益,凝血系统激活有利于血栓的扩大和持续存在,2011,年,ESC,非,ST,段抬高,ACS,诊治指南,所有患者在接受抗血小板治疗的同时应接受抗凝治疗,Anticoagulation is effective in addition to platelet inhibition and that the combination of the two is more effective than either treatment alone-P23,European Heart Journal 2011 Sep 21. ,Epub,ahead of print,2011 ESC,AHA,指南,(NSTE-ACS,抗凝相关,),患者接受抗血小板治疗的同时应接受抗凝治疗,抗凝药物的选择要兼顾疗效和安全性,新增拟行紧急侵入治疗患者的抗凝治疗建议,其他：,不推荐交叉应用普通肝素和,LMWH,“,不仅仅关注,抗凝,疗效和缺血并发症,同时还要注意到出血引发的相关风险,”,Gibbons 354:1524-7,ACS,抗凝治疗应更加关注风险收益率,疗效净受益,收益,血栓事件,风险, 出血,应使用已知在,保证抗凝疗效,的同时,可,降低出血风险,的药物,肝素类、戊糖及水蛭素抗凝作用位点,VIIa,Va,XIa,IXa,Xa,IIa,VIIIa,激活,激活,激活,激活,激活,Mackman,N. NATURE.2008; 451: 914-918,组织因子,普通肝素,低分子肝素,水蛭素,磺达肝癸钠,纤维蛋白原,纤维蛋白,XIIa,OASIS 8:,研究设计,NSTEACS,Fonda 2.5 mg sc,造影,无,PCI,随访,30,天,造影并,PCI,R,标准剂量普通肝素,(85 U/kg,或,60 U/kg,联用,GP IIb/IIIa),ACT,监控,*,随访,30,天,低剂量普通肝素,(50 U/kg,不考虑,GP IIb/IIIa,) ,无,ACT,监控,随访,30,天,符合以下至少两项,:,年龄,60,生物标记物升高,ECG,改变,由于临床病情不稳定，需要紧急冠脉造影,(120 min),的不纳入。,PCI,术中抗凝治疗,双盲,登记,*ACT,监控符合当前指南,拟,72,小时内进行冠状动脉造影,/PCI,JAMA. 2010;304(12),OASIS 8,：,Fonda+,标准剂量,UFH,OASIS 8,与,OASIS 5,大出血事件发生率比较,(,PCI,后,48 h ),大出血发生率,(95% CI),OASIS 5 PCI,磺达肝癸钠,大出血发生率,OASIS 5 PCI,依诺肝素,大出血发生率,FUTURA,标准剂量,UFH,1.2%,1.5%,3.6%,FUTURA,低剂量,UFH,1.4%,Steg,PG,Jolly,SS,Mehta,SR, et,al.JAMA,2010;304:1339-1349.,磺达肝癸钠,+,标准剂量,UFH,大出血发生率显著低于依诺肝素,标准剂量,UFH,：,85IU/kg,；或,60IU/kg(,联用,GP b/a,受体拮抗剂,),低剂量,UFH,：,50IU/kg,，无论是否联用,GP b/a,受体拮抗剂,2011,年,ESC,非,ST,段抬高,ACS,诊治指南,推荐,Class,Level,磺达肝癸钠（,2.5mg/,日,s.c,.,）在抗凝作用上具有最佳的疗效,-,安全性,A,PCI,术前使用磺达肝癸钠患者，,PCI,手术时应使用普通肝素,.85IU/kg,，或,60IU/kg(,联用,GP b/a,受体拮抗剂,),根据,ACT,调整,B,磺达肝癸钠,+UFH,指南,I,级推荐的策略,European Heart Journal 2011 Sep 21. ,Epub,ahead of print,2024/10/5,总结用药方案,术前,术中,术后,紧急,PCI,术,(120,分钟,),_,UFH,常规剂量使用,安卓,2.5mg,每日一次，直至出院,早期,PCI(72,小时,),安卓,2.5mg,每日一次，,1-3,天,UFH 50-100IU/kg,安卓,2.5mg,每日一次，直至出院,择期,PCI,安卓,2.5mg,每日一次，,4-7,天,PCI,术,(UFH 50-100IU/kg),或造影,安卓,2.5mg,每日一次，直至出院或不用药物,保守治疗,入院即处方安卓,2.5mg,每日一次,直至出院,PCI,术后鞘管移除至少,3,小时后恢复安卓用药,2011 ESC,AHA,指南,(NSTE-ACS,抗凝相关,),患者接受抗血小板治疗的同时应接受抗凝治疗,抗凝药物的选择要兼顾疗效和安全性,新增拟行紧急侵入治疗患者的抗凝治疗建议,其他：,不推荐交叉应用普通肝素和,LMWH,ACS,患者,PCI,术中,抗凝药物选择,普通肝素,比伐卢定,依诺肝素,PCI,手术期间,70-100IU/kg,，,根据,ACT,调整,(250s-350s),；,50-60IU/kg,(,联用,GP b/a,受体拮抗剂,),根据,ACT,调整,(200s-250s),单独使用,:,根据,APTT,调整,( 50s-70s),NSTE-ACS,：,0.5mg/kg,i.v,. bolus,(+0.3mg/kg if needed),increase to 1.75mg/kg/h before PCI,STE-ACS,:,0.75mg/kg bolus,(+0.3mg/kg if needed),followed by 1.75mg/kg/h,GFR30-60ml/min/1.73m,2,:,1.0mg/kg/h,术前末次依诺肝素,12,小时,:,0.75-1.0 mg/kg,i.v,.,提示,:,术前需按患者公斤体重计算给药,患者,75,岁,1mg/kg q12h sc.,患者,75,岁,0.75mg/kg q12h sc.,Ccr,30ml/min,1mg/kg,qd,sc.,2011,年,ESC,非,ST,段抬高,ACS,诊治指南,2010,年,ESC,心肌血运重建指南,Lovenox,Label-FDA 2008 revised,比伐卢定、依诺肝素、普通肝素,防止心导管内血栓形成的作用比较,Thromb Haemost 2008;100:693-698,2008,年,德国,Martin Luther-University.,10,位健康志愿者,7,组不同抗凝药物,.,服用,Asprin,500mg,后,2,小时抽取,50ml,静脉血,.,重复取血,7,次,.,37,度恒温下,:,将静脉血和抗凝药物混合后,在,6F,导管中持续循环,60,分钟或直至导管因血栓堵塞,.,用减重法测量血栓重量,.,灌洗导管后,用电子显微镜观察附着在心导管内壁的血小板,纤维蛋白和红细胞,灌流时间：普通肝素，比伐卢定与依诺肝素相似,导管经灌洗后,附着于内壁的的纤维蛋白及红细胞评估：,UFH,，比伐卢定优于依诺肝素,7,组抗凝药物导管附着物的电镜扫描：,UFH,，,Bivalirudin,避免心导管内细胞附着作用确切,扫描电镜,:LEO1530 scanning electron,microscope,Gatech,Georgia,USA,Thromb Haemost 2008;100:693-698,2011ACCF/AHA/SCAI Guideline for PCI,Circulation. 2011;124:,UFH,和,Bivalirudin,是导管室抗凝药物的首选,2011 ESC,AHA,指南,(NSTE-ACS,抗凝相关,),患者接受抗血小板治疗的同时应接受抗凝治疗,抗凝药物的选择要兼顾疗效和安全性,新增拟行紧急侵入治疗患者的抗凝治疗建议,其他：,不推荐交叉应用普通肝素和,LMWH,ACS,抗凝领域现状的思考,LMWH,是,ACS,患者抗凝的常规选择,PCI,术中使用,UFH,是绝大多数中国医生的选择,围,PCI,手术期出现了,LMWH,与,UFH,交叉的问题,SYNERGY,研究表明交替使用,LMWH,和,UFH,会增加出血风险,指南指出,LMWH,与,UFH,不能交叉使用,是否会增加出血风险？,循证与指南,现状,SYNERGY,研究,:ACS,治疗中,LMWH,与,UFH,交叉使用：,增加出血风险,TIMI,大出血,GUSTO,严重出血,(n = 8873),(n =740),(n = 9613),(n = 8873),(n =740),JAMA: 2004. 292:45-54,依诺肝素,普通肝素,P=0.008,SYNERGY,研究,: ACS,抗凝治疗中,LMWH,与,UFH,交叉使用,:,死亡,/,梗死率增加,(n = 9978),(n = 9180),(n =798),JAMA: 2004. 292:45-54,依诺肝素,（,n=4993,）,普通肝素,（,n= 4985,）,30,天死亡,/,心梗,%,死亡,/,心肌梗死,OR 0.96,95%Cl 0.86-1.06,OR 0.95,95%Cl 0.85-1.06,OR 0.76,95%Cl 0.53-1.09,Synergy,研究亚组分析结论,Overall,it,appears that changing,antithrombin,therapy during the treatment course is not associated with any treatment benefit and is associated with an increased risk of bleeding,在非,ST,段抬高的急性冠脉综合征的治疗过程中,交替使用抗凝药物没有任何疗效方面的获益,同时增加出血风险,.,SYNERGY Trial,Investigators.JAMA,. 2004;292(1):45-54,STACKENOX,研究,依诺肝素和,UFH,不宜交叉使用,研究方案,检测指标,ACT,:,活化凝血时间，反应内源性凝血，常用于体外循环监测肝素抗凝效果。,Anti,Xa,activities,:,抗,Xa,因子活性，常用于评估抗凝水平。,ETP,:,内生性凝血酶能力，评估凝血酶的产生。,Drouet,L,et,al.Am,Heart J.2009 Aug;158(2):177-84.,在标准剂量的依诺肝素基础上,静脉添加,UFH,测凝血指标,皮下注射依诺肝素后,4,6,10,小时静脉添,UFH(70IU/kg),均导致,ACT,无法探查的过度抗凝,添加,UFH,后抗,Xa,水平超过治疗范围,ACT,处于治疗范围,Drouet,L,et,al.Am,Heart J.2009 Aug;158(2):177-84.,In NSTE-ACS patients pre-treated with,enoxaparin,Crossing over to another anticoagulant during PCI is strongly discouragedIII,B,P26,28,European Heart Journal 2011 Sep 21. ,Epub,ahead of print,Circulation. 2011;124,2011,年,ESC,非,ST,段抬高,ACS,诊治指南,2011ACCF/AHA/SCAI Guideline for PCI,Patients treated with SC,enoxaparin,within 12h of PCI should not receive additional treatment with UFH during PCI,ClassIII:Harm;LOE:B,.,-page14,普通肝素勿与依诺肝素交叉使用,2011,年,ESC,非,ST,段抬高,ACS,诊治指南,推荐,Class,Level,磺达肝癸钠（,2.5mg/,日,s.c,.,）在抗凝作用上具有最佳的疗效,-,安全性,A,PCI,术前使用磺达肝癸钠患者，,PCI,手术时应使用普通肝素,.,85IU/kg,，或,60IU/kg,(,联用,GP b/a,受体拮抗剂,),根据,ACT,调整,B,指南推荐,磺达肝癸钠,+UFH,European Heart Journal 2011 Sep 21. ,Epub,ahead of print,Benefit,thrombotic events,Risk,bleeding,Bivalirudin,Fondaparinux,Thrombin receptor antagonists (?),A paradigm shift,Balancing Risk and Benefit,Aspirin,ADP antagonist,GPIIb/IIIa antagonist,Enoxaparin,2011,年,ESC,非,ST,段抬高,ACS,诊治指南,抗凝部分,推 荐,Class,Level,Anticoagulation is recommended for all patients in addition to,antiplatelet,therapy,A,The anticoagulation should be selected according to both,ischaemic,and bleeding,risks,and,according to the,efficacy-safety,profile of the chosen agent.,I,C,Fondaparinux,（,2.5mg,s.c.daily,）,is recommended as having the most,favourable,efficacy-safety profile with respect to anticoagulation.,A,If the initial anticoagulant is,fondaparinux,a,single bolus of UFH(85IU/kg adapted to,ACT,or,60IU in the case of concomitant use of GP b/a receptor,inhibitors)should,be added at the time of PCI,B,Enoxaparin,（,1mg/kg twice daily,）,is recommended when,fondaparinux,is not available,B,In a purely,conservative,strategy,anticoagulation,should be maintained up to hospital discharge,I,A,Discontinuation of anticoagulation should be considered,after an invasive,procedure unless otherwise indicated,IIa,C,Crossover of,heparins(UFH,and,LMWH)is,not recommended,B,小结,对于,ACS,患者,第一时间接受抗凝治疗和抗血小板治疗同样重要,目前,UFH,是,PCI,术中广泛使用的抗凝药物,依诺肝素应避免与其交叉使用,磺达肝癸钠联合,UFH,是结合了循证,指南和临床实践的抗凝方案,谢谢！,
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