急性冠脉综合征抗栓治疗PPT(最新版)课件

急性冠脉综合征抗栓治疗急性冠脉综合征抗栓治疗1（优选）急性冠脉综合征抗栓治疗（优选）急性冠脉综合征抗栓治疗2肝素肝素IIaXa513 ATIII ATIII135 IIa ATIIILMWH510 ATIII Xa三种肝素三种肝素类药物抗凝机制物抗凝机制对比比戊糖5 ATIII5 ATIII Xa510肝素IIaXa513 ATIII ATIII1353低分子肝素和肝素抗凝区别低分子肝素和肝素抗凝区别肝素和低分子肝素抗肝素和低分子肝素抗Xa因子和抗因子和抗IIa因子活性随因子活性随着分子量的着分子量的变化而改化而改变Anti-Xa activityAnti-Xa activityAnti-IIa activityAnti-IIa activity.5,00010,00015,000 20,0002001000MWAcivity(U/mg)IIaIIaXaXaIIaIIaXaXa1:11:1肝素肝素肝素肝素1:1:-LMLMWHWH低分子肝素和肝素抗凝区别肝素和低分子肝素抗Xa因子和抗IIa4肝素结果总结肝素结果总结10%5%015%250300350400450激活的凝血时间激活的凝血时间头头 7-天事件发生率天事件发生率Abciximab+肝素出血肝素出血肝素出血肝素出血Abciximab+肝素肝素death/MI/revasc.肝素肝素death/MI/revasc.肝素结果总结10%5%015%2503003504004505肝素最适肝素最适 ACT 对有效性单纯肝素 350+秒和 GP2b3a 无关对安全性单纯肝素 300 秒和 GP2b3a 225 秒肝素最适 ACT 对有效性6普通肝素存在的普通肝素存在的问题不确定的不确定的剂量反量反应性性 -血浆结合蛋白血浆结合蛋白血浆结合蛋白血浆结合蛋白 -同时使用同时使用同时使用同时使用 IV IV 硝酸甘油硝酸甘油硝酸甘油硝酸甘油,DIC,DIC肝素抵抗有天然抑制肝素抵抗有天然抑制剂 -(PF4)(PF4)不能抑制不能抑制结合于血栓的凝血合于血栓的凝血酶 不规则病变引发凝血酶生成不规则病变引发凝血酶生成不规则病变引发凝血酶生成不规则病变引发凝血酶生成剂量量过高，清除半衰期延高，清除半衰期延长需要需要实验室室监测普通肝素存在的问题不确定的剂量反应性7由于肝素作用失败使患者处于由于肝素作用失败使患者处于血栓形成风险中血栓形成风险中由于肝素作用失败使患者处于血栓形成风险中8肝素用于高危肝素用于高危 PCI肝素作用钝化，当肝素作用钝化，当凝血酶和纤维蛋白结合凝血酶和纤维蛋白结合循环中循环中 PF-4 抑制肝素作用抑制肝素作用高剂量导致血小板聚集高剂量导致血小板聚集典型患者人群典型患者人群既往使用过肝素治疗既往使用过肝素治疗既往存在血栓形成既往存在血栓形成(MI后后)急性冠状动脉综合症急性冠状动脉综合症(使用肝素使用肝素)肝素用于高危 PCI肝素作用钝化，当9肝素在肝素在 ACS 中反应钝化中反应钝化Wilson et al 1995激活的凝血时间对激活的凝血时间对 10,000 单位肝素发生反应单位肝素发生反应肝素在 ACS 中反应钝化Wilson et al 199510抗因子 Xa:IIa生物利用度监测 ACT 对PF4敏感 No High 1 No Yes Low=1 Yes 为什么在 PCI 中使用LMWH?LMWHATATXaXaUFHATATIIaIIaHepHep抗因子 Xa:IIa生物利用度监测 ACT 对PF4敏感 N11 优点：优点：优点：优点：使用方便、半衰期长使用方便、半衰期长更有效抑制更有效抑制 Xa减少凝血酶原减少凝血酶原、减少反弹、减少反弹较少免疫反应较少免疫反应、减少、减少HIT和和GP IIb/IIIa抑制剂合用出血抑制剂合用出血可能减少可能减少 只证明依诺肝素优于普通肝素只证明依诺肝素优于普通肝素具有成本效益具有成本效益 缺点：缺点：缺点：缺点：难以检测难以检测(?necessary)用拮抗药不能完全逆转用拮抗药不能完全逆转注射部位瘀斑注射部位瘀斑可能更多的出血可能更多的出血在特殊人群中潜在危险，在特殊人群中潜在危险，如肾功能不全的病人如肾功能不全的病人、超重的病人超重的病人直接成本增加直接成本增加为什么在什么在 PCI 中使用中使用LMWH?优点：缺点：为什么在 PCI 中使用LMWH?12LMWH取代取代UFH?!NSTE ACS STE ACSPCIVTE+?+?+STEEPLELMWH取代UFH?!NSTE ACS +133030天死亡或心梗天死亡或心梗天死亡或心梗天死亡或心梗非非非非STST 段抬高急性心梗患者随机接受段抬高急性心梗患者随机接受段抬高急性心梗患者随机接受段抬高急性心梗患者随机接受依诺肝素或普通肝素的疗效依诺肝素或普通肝素的疗效依诺肝素或普通肝素的疗效依诺肝素或普通肝素的疗效PetersenPetersen.JAMA JAMA 2004;2004;292292:89968996TrialTrialEnoxaparinEnoxaparinUFHUFHOR(95%CI)OR(95%CI)FavorsFavorsEnoxaparinEnoxaparinFavorsFavorsUFHUFHEvents,No./Total(%)Events,No./Total(%)0.20.21.01.02.02.0OROR(95%CI)(95%CI)ESSENCEESSENCE0.760.76(0.58-1.01)(0.58-1.01)94/160794/1607(5.8)(5.8)118/1564118/1564(7.5)(7.5)TIMI 11BTIMI 11B0.880.88(0.70-1.11)(0.70-1.11)145/1953145/1953(7.4)(7.4)163/1957163/1957(8.6)(8.6)ACUTE IIACUTE II0.970.97(0.51-1.83)(0.51-1.83)25/31525/315(7.9)(7.9)17/21017/210(8.1)(8.1)INTERACTINTERACT0.540.54(0.30-0.96)(0.30-0.96)19/38019/380(5.0)(5.0)33/36633/366(9.0)(9.0)A to ZA to Z0.940.94(0.73-1.20)(0.73-1.20)137/1852137/1852(7.4)(7.4)139/1768139/1768(7.9)(7.9)SYNERGYSYNERGY0.960.96(0.86-1.07)(0.86-1.07)696/4992696/4992(14.0)(14.0)722/4982722/4982(14.5)(14.5)OVERALLOVERALL0.910.91(0.83-0.99)(0.83-0.99)1116/110991116/11099(10.1)(10.1)1192/108471192/10847(11.0)(11.0)30天死亡或心梗非ST 段抬高急性心梗患者随机接受Peter14安全性分析安全性分析安全性分析安全性分析随机化随机化随机化随机化7 7天后所有人群的严重出血情况天后所有人群的严重出血情况天后所有人群的严重出血情况天后所有人群的严重出血情况PetersenPetersen.JAMA JAMA 2004;2004;292292:89968996TrialTrialEnoxaparinEnoxaparinUFHUFHOR(95%CI)OR(95%CI)FavorsFavorsEnoxaparinEnoxaparinFavorsFavorsUFHUFHEvents,No./Total(%)Events,No./Total(%)0.20.21.01.02.02.0OROR(95%CI)(95%CI)ESSENCEESSENCE0.900.90(0.63-1.27)(0.63-1.27)64/157864/1578(4.1)(4.1)69/152969/1529(4.5)(4.5)TIMI 11BTIMI 11B1.521.52(0.85-2.70)(0.85-2.70)29/193829/1938(1.5)(1.5)19/193619/1936(1.0)(1.0)INTERACTINTERACT0.470.47(0.24-0.95)(0.24-0.95)12/38012/380(3.2)(3.2)24/36624/366(6.6)(6.6)SYNERGYSYNERGY1.171.17(0.99-1.39)(0.99-1.39)276/4148276/4148(6.7)(6.7)274/4775274/4775(5.7)(5.7)OVERALLOVERALL1.041.04(0.89-1.30)(0.89-1.30)381/8044381/8044(4.7)(4.7)386/8606386/8606(4.5)(4.5)安全性分析Petersen.JAMA 2004;292:815To summarizeVery Low risk Very Low risk Very Low risk Medium to High risk Medium to High risk Medium to High risk High to Very High Risk High to Very High Risk High to Very High Risk Use only ASAUse only ASAUse only ASANo indication for No indication for No indication for Enoxaparin or Enoxaparin or Enoxaparin or UFHUFHUFHESSENCE&TIMI 11BESSENCE&TIMI 11BESSENCE&TIMI 11BEnoxaparin is Enoxaparin is Enoxaparin is superior to UFHsuperior to UFHsuperior to UFHUA/NSTEMI UA/NSTEMI patientspatientsLater Invasive Later Invasive Later Invasive or Conservative or Conservative or Conservative ManagementManagementManagementVery Early Invasive Very Early Invasive Very Early Invasive ManagementManagementManagementSYNERGYSYNERGYSYNERGYEnoxaparin no Enoxaparin no Enoxaparin no better than UFHbetter than UFHbetter than UFHHigher bleeding Higher bleeding Higher bleeding with enoxaparinwith enoxaparinwith enoxaparinINTERACTINTERACTINTERACTEnoxaparin is Enoxaparin is Enoxaparin is superior to UFHsuperior to UFHsuperior to UFHA to ZA to ZA to ZEnoxaparin no better Enoxaparin no better Enoxaparin no better than UFHthan UFHthan UFHTo summarizeVery Low risk Medi16与免疫相关药物副反应，产生针对血小板因子（PF）-4和肝素复合物的抗体，可视作医源性损害之一。High to Very High RiskOR(95%CI)在STEMI的病人中给予溶栓治疗，与UFH相比LMWH:Dyspepsia or GERD symptoms肝素和低分子肝素抗Xa因子和抗IIa因子活性随着分子量的变化而改变抗血小板聚集，应用凝血酶直接抑制剂（DTI）和抗Xa制剂以降低血栓形成风险Fondaparinux:Enoxaparin is superior to UFH只证明依诺肝素优于普通肝素30天的心血管死亡或心肌梗死Hb是心血管不良事件的独立预测因子（Arant等）单纯肝素 350+秒The recommended ACT with no planned GP IIb/IIIa receptor antagonist treatment is 250 to 300 s(HemoTec device)or 300 to 350 s(Hemochron device).Fondaparinux:OR(95%CI)在随后的PCI中有效；Aged 60 years or moreSarnak MJ.No indication for Enoxaparin or UFHLMWH在在ST抬高的抬高的ACS中低分子肝素和中低分子肝素和普通肝素普通肝素应用用对比比与免疫相关药物副反应，产生针对血小板因子（PF）-4和肝素复1730天的心血管死亡或心肌梗死天的心血管死亡或心肌梗死UFHUFHLMWHLMWHP=0.030P=0.030Adj Odds Ratio 0.68Adj Odds Ratio 0.68(95%CI 0.48-0.96)(95%CI 0.48-0.96)n=1429n=1431Adjusted for type of lytic,infarct location,h/o HTN,cardiac medications,time to angiography,and propensity score for LMWH use.Sabatine et al.Circulation 200530天的心血管死亡或心肌梗死UFHLMWHP=0.030Ad18总结：在在在在STEMISTEMI的病人中给予溶栓治疗，与的病人中给予溶栓治疗，与的病人中给予溶栓治疗，与的病人中给予溶栓治疗，与UFHUFH相比相比相比相比LMWHLMWH :使动脉闭塞或死亡心肌梗死使动脉闭塞或死亡心肌梗死降低降低降低降低 24%24%；使使使使3030天的心血管死亡或心肌梗死降低天的心血管死亡或心肌梗死降低天的心血管死亡或心肌梗死降低天的心血管死亡或心肌梗死降低32%32%；在随后的在随后的在随后的在随后的PCIPCI中有效；中有效；中有效；中有效；并不增加并不增加并不增加并不增加TIMI TIMI 大出血、小出血或颅内出血。大出血、小出血或颅内出血。大出血、小出血或颅内出血。大出血、小出血或颅内出血。总结：在STEMI的病人中给予溶栓治疗，与UFH相比LMWH19肝素诱导的血小板减少症肝素诱导的血小板减少症Heparin-induced thrombocytopeniaMyth or reality?肝素诱导的血小板减少症Heparin-induced th20HIT定定义 Heparin-Induced Thrombocytopenia 肝素诱导血小板减少症肝素诱导血小板减少症n多见于肝素治疗第多见于肝素治疗第5-14天，血小板计数相对值下降天，血小板计数相对值下降50或绝对值或绝对值降至降至50-80109/L，停药后，停药后4-14天恢复正常天恢复正常。n与免疫相关药物副反应，产生针对血小板因子（与免疫相关药物副反应，产生针对血小板因子（PF）-4和肝素复和肝素复合物的抗体，可视作医源性损害之一。合物的抗体，可视作医源性损害之一。HIT定义 Heparin-Induced Thro21型型HIT型型HIT发生频率发生频率10-202-30发生时间发生时间1-3d（大剂量肝素）（大剂量肝素）5-14d（各剂量各途径）（各剂量各途径）血小板计数血小板计数100-150109/L50-80109/L抗体存在抗体存在否否是是血栓形成血栓形成无无30-80%出血表现出血表现无无罕见罕见处理原则处理原则观察观察停肝素，选择其他抗凝停肝素，选择其他抗凝药物替代药物替代HIT临床分型床分型型HIT型HIT发生频率10-202-30发生时间122HIT治治疗高度警惕，早诊早治高度警惕，早诊早治停用停用UFH和和LMWH，避免一切潜在肝素来源，避免一切潜在肝素来源抗血小板聚集，应用凝血酶直接抑制剂（抗血小板聚集，应用凝血酶直接抑制剂（DTIDTI）和抗）和抗XaXa制剂以制剂以降低血栓形成风险降低血栓形成风险不提倡输注血小板，避免早期使用华法林不提倡输注血小板，避免早期使用华法林对单纯血小板减少者，治疗至血小板计数恢复后对单纯血小板减少者，治疗至血小板计数恢复后2-4周；对血周；对血栓形成者则持续栓形成者则持续3-6月月HIT治疗高度警惕，早诊早治23急性冠脉综合征抗栓治疗PPT(最新版)课件24Fondaparinux:In UA/NSTEMI(OASIS5)在在NSTE ACS病人中，病人中，Fondaparinux 和依诺肝素和依诺肝素对照研究对照研究Fondaparinux:In UA/NSTEMI(OAS25急性冠脉综合征抗栓治疗PPT(最新版)课件26Death,MI,revasc-血浆结合蛋白Enoxaparin is superior to UFH强调正确评价肾功能，患者血肌酐水平不能反应肾功能，应该计算肌酐清除率。OR(95%CI)The recommended ACT with planned GP IIb/IIIa receptor antagonist treatment is 200 to 250 s.大出血治疗策略-中和抗栓药物Anti-IIa activity依诺肝素或普通肝素的疗效BivalirudinATIII与免疫相关药物副反应，产生针对血小板因子（PF）-4和肝素复合物的抗体，可视作医源性损害之一。不提倡输注血小板，避免早期使用华法林ATIIIEnoxaparin administered according to age,weight,and creatinine clearance,given as an intravenous bolus,followed in 15 minutes by subcutaneous injection for the duration of the index hospitalization,up to 8 days or until revascularization;orThe recommended ACT with no planned GP IIb/IIIa receptor antagonist treatment is 250 to 300 s(HemoTec device)or 300 to 350 s(Hemochron device).appropriate dosage(according age,sex,and CrCl)依诺肝素或普通肝素的疗效Eur Heart J 2003;24:1815-23.Bivalirudin组死亡率有降低趋势。与依诺肝素相比，与依诺肝素相比，fondaparinux治疗治疗1000 NSTE ACS 病病人预防人预防:10 deaths or MI 4 strokes 25 major bleeds明显降低明显降低1个月和个月和6个月的死亡率个月的死亡率显著降低严重出血并发症显著降低严重出血并发症在在PCI 病人中并不比依诺肝素差病人中并不比依诺肝素差OASIS 5总结Death,MI,revasc与依诺肝素相比，fonda27Fondaparinux:STEMI 病人在症状发作的病人在症状发作的12 h内内Fondaparinux和普和普通肝素对照研究。通肝素对照研究。OASIS 6ACC 2006Fondaparinux:STEMI 病人在症状发作的12 28急性冠脉综合征抗栓治疗PPT(最新版)课件29急性冠脉综合征抗栓治疗PPT(最新版)课件30急性冠脉综合征抗栓治疗PPT(最新版)课件31 3 important areas:1.Active site:fibrinogen binding2.Exosite I:major docking site-interaction with fibrinogen and other receptors;fibrinogen recognition site3.Exosite II:interacts with heparinThrombin 3 important areas:Thromb32Hirudin医学上的水蛭病医学上的水蛭病古时候埃及人和希古时候埃及人和希腊人用于解除身体腊人用于解除身体上的上的“坏体液坏体液”在在1919世纪中期最盛世纪中期最盛行行Hirudo medicinalisHirudin医学上的水蛭病Hirudo medicinal33Bivalirudin 模拟天然模拟天然水蛭素水蛭素Gly-Pro-Arg-Pro(active site binding region)(Gly)4C-terminal dodecapeptide(exosite 1-binding region)Bivalirudin 模拟天然水蛭素Gly-Pro-Ar347天时发生事件患者%出血出血Death,MI,revascUnstable&MI后后n=241Unstable 用肝素用肝素n=1,006MI后后n=741没有危没有危险因素险因素n=2,806Heparin16.5%14.0%Heparin11.8%9.9%Bivalirudin3.3%5.8%Bivalirudin2.4%4.9%Bivalirudin3.8%6.1%Bivalirudin4.1%7.4%Heparin11.9%10.3%Bivalirudin 用于用于 PCI 的结果的结果 特定高危人群的初步结果特定高危人群的初步结果Heparin8.3%7.0%Heparin7天时发生事件患者%出血Death,MI,revasc35Quadruple Endpoint 30 Day Primary Endpoint Components30 Day Primary Endpoint Componentsp 0.001LincoffQuadruple Endpoint 30 Day Prim36Fondaparinux:强调正确评价肾功能，患者血肌酐水平不能反应肾功能，应该计算肌酐清除率。2004;43:20092014.Eur Heart J 2003;24:1815-23.Bivalirudin在随后的PCI中有效；0g/L，心血管事件危险降低20Patients with STEMI undergoing reperfusion with fibrinolytic therapy should receive anticoagulant therapy for a minimum of 48 hours,and preferably for the duration of the index hospitalization,up to 8 days or until revascularization if performed.Circulation 2005Abciximab+肝素Events,No.The recommended ACT with no planned GP IIb/IIIa receptor antagonist treatment is 250 to 300 s(HemoTec device)or 300 to 350 s(Hemochron device).Death,MI,revascAbciximab+肝素High to Very High Risk累计事件发生率(%)Protamine sulfate has less impact on the neutralization of enoxaparin and has no effect on fondaparinux or bivalirudin.Enoxaparin administered according to age,weight,and creatinine clearance,given as an intravenous bolus,followed in 15 minutes by subcutaneous injection for the duration of the index hospitalization,up to 8 days or until revascularization;or发生消化道出血时，应积极处理局部出血灶（内镜下止血），尽量不停用抗血小板治疗。与依诺肝素相比，fondaparinux治疗1000 NSTE ACS 病人预防:REPLACE-2Bivalirudin 能明显减少临床事件的发生率；能明显减少临床事件的发生率；明显降低住院期间的出血率；明显降低住院期间的出血率；两组间两组间MI、紧急血运重建等终点事件的发生率、紧急血运重建等终点事件的发生率相等；相等；Bivalirudin组死亡率有降低趋势。组死亡率有降低趋势。结论在在PCI中，病人被随机分为中，病人被随机分为bivalirudin或肝素或肝素+GP IIb/IIIa抑制剂治疗：抑制剂治疗：Fondaparinux:REPLACE-2结论在PCI中，37Adjunctive Anticoagulant Therapy With FibrinolysisPatients with STEMI undergoing reperfusion with fibrinolytic therapy should receive anticoagulant therapy for a minimum of 48 hours,and preferably for the duration of the index hospitalization,up to 8 days or until revascularization if performed.Recommended regimens include:a.UFH administered as a weight-adjusted intravenous bolus and infusion to obtain an activated partial thromboplastin time of 1.5 to 2.0 times control,for 48 hours or until revascularization;b.Enoxaparin administered according to age,weight,and creatinine clearance,given as an intravenous bolus,followed in 15 minutes by subcutaneous injection for the duration of the index hospitalization,up to 8 days or until revascularization;or c.Fondaparinux administered with initial intravenous dose,followed in 24 hours by daily subcutaneous injections if the estimated creatinine clearance is greater than 30 mL/min,for the duration of the index hospitalization,up to 8 days or until revascularization.I IIa IIb IIII IIa IIb IIII IIa IIb IIII IIa IIb III2013 ACCF/AHA GuidelineAdjunctive Anticoagulant Thera38Adjunctive Antithrombotic Therapy to Support Reperfusion With Primary PCIThe recommended ACT with planned GP IIb/IIIa receptor antagonist treatment is 200 to 250 s.The recommended ACT with no planned GP IIb/IIIa receptor antagonist treatment is 250 to 300 s(HemoTec device)or 300 to 350 s(Hemochron device).2013 ACCF/AHA GuidelineAdjunctive Antithrombotic Ther39出血对预后的影响出血对预后的影响405.15.13.03.05.35.37.07.018.618.616.116.115.315.322.822.80 010102020303040405050总体总体不稳定心绞痛不稳定心绞痛非非ST段抬高型段抬高型MIST段抬高型段抬高型MI患者患者院内死亡率院内死亡率 (%)(%)未大出血未大出血大出血大出血*P P0.0010.001*Moscucci M et al.Eur Heart J 2003;24:1815-23.大出血患者院内死亡率大出血患者院内死亡率5.13.05.37.018.616.115.322.80141基于出血的30天死亡事件OASIS、OASIS-2及CURE研究(n=34 146)Eikelboom Circulation 2006;114:774-782;published online August 14 2006 风险风险 5倍倍 02468101214051015202530出血出血未出血未出血累计事件发生率累计事件发生率(%)33676334193315732990328793276932710470459440430420410408天天风险患者例数风险患者例数未出血未出血出血出血基于出血的30天死亡事件OASIS、OASIS-2及C42贫血对贫血对ACSACS预后预测价值预后预测价值Hb是心血管不良事件的独立预测因子（Arant等）-Hb每增加1.0g/L，心血管事件危险降低20 -有贫血的人群发生心血管事件的危险比无贫血的人群增加41 Arant CB.J Am Coll Cardiol.2004;43:20092014.Sarnak MJ.J Am Coll Cardiol.2002;40:2733.贫血对ACS预后预测价值Hb是心血管不良事件的独立预测因子 43输血患者预后不良输血患者预后不良44输血组输血组3030天的生存率：天的生存率：GUSTO IIbGUSTO IIb、PURSUITPURSUIT及及 PARAGON BPARAGON B研究研究 (n=24 000;10%(n=24 000;10%输血输血)-Rao SV,et.al.,JAMA 20040.90.920.940.960.98105101520253035时间（天）时间（天）生存率生存率未输血未输血输血输血输血组30天的生存率：GUSTO IIb、PURSUIT及45冠心病出血、输血与预后的观点1.出血导致死亡和出血导致死亡和MI风险增加风险增加2.预防出血与预防缺血事件同等重要预防出血与预防缺血事件同等重要3.输血可能有潜在危害输血可能有潜在危害4.只有在发生致命性贫血只有在发生致命性贫血(红细胞压积低于红细胞压积低于 25%)时才应时才应输血输血 冠心病出血、输血与预后的观点出血导致死亡和MI风险增加46为什么在 PCI 中使用LMWH?贫血对ACS预后预测价值Bivalirudin4 strokesPatients with STEMI undergoing reperfusion with fibrinolytic therapy should receive anticoagulant therapy for a minimum of 48 hours,and preferably for the duration of the index hospitalization,up to 8 days or until revascularization if performed.Medium to High riskAbciximab+肝素OR(95%CI)古时候埃及人和希腊人用于解除身体上的“坏体液”4 strokesDyspepsia or GERD symptomsDyspepsia or GERD symptoms在随后的PCI中有效；Protamine sulfate has less impact on the neutralization of enoxaparin and has no effect on fondaparinux or bivalirudin.Active site:fibrinogen bindingHeparin-Induced ThrombocytopeniaBivalirudin出血导致死亡和MI风险增加OR(95%CI)J Am Coll Cardiol.出血风险评估出血风险评估推荐两个常用出血危险评估系统：推荐两个常用出血危险评估系统：GRACE出血评分系统和出血评分系统和CRUSADE出血评分系统来评估患者的出血风险。出血评分系统来评估患者的出血风险。严重出血独立危险因素包括高龄、女性、出血病史、严重出血独立危险因素包括高龄、女性、出血病史、PCI、肾功能、肾功能不全病史及使用不全病史及使用GPb/a受体拮抗剂。受体拮抗剂。强调正确评价肾功能，患者血肌酐水平不能反应肾功能，应该计算强调正确评价肾功能，患者血肌酐水平不能反应肾功能，应该计算肌酐清除率。肌酐清除率。为什么在 PCI 中使用LMWH?出血风险评估推荐两个常用出47预防出血原则Prevention of bleeding encompasses the choice of：n safer drugsnappropriate dosage(according age,sex,and CrCl)n reduced duration of antithrombotic treatment预防出血原则Prevention of bleeding e48Safer drugsConsistent UFH/EnoxaparinBivalirudinFondaparimuxAntiplatelet drugsSafer drugsConsistent UFH/Enox49急性冠脉综合征抗栓治疗PPT(最新版)课件50大出血治大出血治疗策略策略-中和抗凝中和抗凝药物物大出血治疗策略-中和抗凝药物51大出血治大出血治疗策略策略-中和抗栓中和抗栓药物物UFH can be inhibited by an equimolar concentration of protamine sulfate.Protamine sulfate has less impact on the neutralization of enoxaparin and has no effect on fondaparinux or bivalirudin.Bivalirudin has a very short half-life,with the result that it may not be necessary to neutralize it.In the case of fondaparinux,recombinant factor VIIa has been recommended,but is associated with an increased risk of thrombotic complications.301There is no known antidote to irreversible antiplatelet agents such as aspirin,clopidogrel,or prasugrel.Therefore,their action can be neutralized only by transfusion of fresh platelets.This is largely the same for ticagrelor shortly(3 days)after withdrawal of the drug.大出血治疗策略-中和抗栓药物UFH can be inhi52大出血治大出血治疗策略策略输血原血原则大出血治疗策略输血原则53小出血治疗原则小出血治疗原则小出血治疗原则54消化道出血治疗消化道出血治疗消化道出血治疗55Algorithm to Assess GI Risk With Antiplatelet TherapyYesYesYesNoNoPPIYesYesYesYesBhatt DL,Scheiman J,Abraham NS,et al.Circulation 2008.Need for antiplatelet therapyAssess GI risk factorsTest for H pylori;treat if infectedHistory of ulcer complication History of ulcer disease(nonbleeding)Dual antiplatelet therapyConcomitant anticoagulantMore than one risk factor:Aged 60 years or moreCorticosteroid useDyspepsia or GERD symptomsAlgorithm to Assess GI Risk Wi56Bivalirudin组死亡率有降低趋势。2013 ACCF/AHA Guideline7天时发生事件患者%Medium to High riskHigh to Very High RiskNeed for antiplatelet therapy明显降低住院期间的出血率；ATIIIOR(95%CI)不提倡输注血小板，避免早期使用华法林JAMA 2004;292:8996Hb是心血管不良事件的独立预测因子（Arant等）Eur Heart J 2003;24:1815-23.难以检测(?necessary)大出血治疗策略输血原则不能抑制结合于血栓的凝血酶2002;40:2733.OR(95%CI)权衡利弊选择 BMSAdjunctive Antithrombotic Therapy to Support Reperfusion With Primary PCIHb是心血管不良事件的独立预测因子（Arant等）肝素和低分子肝素抗Xa因子和抗IIa因子活性随着分子量的变化而改变High to Very High RiskBivalirudin推荐两个常用出血危险评估系统：GRACE出血评分系统和CRUSADE出血评分系统来评估患者的出血风险。ATIII单纯肝素 350+秒Eikelboom Circulation 2006;114:774-782;published online August 14 2006Death,MI,revasc在STEMI的病人中给予溶栓治疗，与UFH相比LMWH:为什么在 PCI 中使用LMWH?既往存在血栓形成(MI后)OR(95%CI)Myth or reality?safer drugsBivalirudinAnti-IIa activity大出血治疗策略输血原则为什么在 PCI 中使用LMWH?在随后的PCI中有效；发生消化道出血生消化道出血时，应积极极处理局部出血灶（内理局部出血灶（内镜下止血），尽下止血），尽量不停用抗血小板治量不停用抗血小板治疗。权衡利弊衡利弊选择 BMS 给药间隔隔时间：PPI间隔隔12小小时可能可能对氯吡格雷的影响吡格雷的影响较小小Antiplatelet and/or anticoagulation agents should not be reintroduced until strict control of the haemorrhage has been obtained for at least 24 h消化道出血治消化道出血治疗Bivalirudin组死亡率有降低趋势。Hb是心血管不良事57