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1、ST抬高心肌梗死溶栓与抗栓治疗-2009进展,西安交通大学医学院第一附属医院心内科 袁祖贻,急性ST段抬高心梗治疗目标,恢复心肌水平再灌注尽早、完全、持续,降低死亡率改善预后,Yusuf S,et al.Circulation.1990;82(suppl II):II-117-II-134.Schrder R,et al.J Am Coll Cardiol.1995;26:1657-1664.,时间就是心肌！时间就是生命！,Symptom Recognition,Call to Medical System,ED,Cath Lab,PreHospital,Delay in Initiation
2、 of Reperfusion Therapy,Increasing Loss of Myocytes,Treatment Delayed is Treatment Denied,溶栓治疗？直接 PCI？,STEMI病人，应采取何种再灌注策略：,溶栓 vs 直接 PCI,溶栓血流TIMI 3 比例60%再梗死发生率 4%卒中总发生率 2%ICH发生率 1%任何地点(院前)任何时间所有医生无时间延迟大规模临床试验证实,直接PCI血流TIMI 3 比例80-90%再梗死发生率 1h),评估STEMI再灌注方式 ACC/AHA 2007 STEMI Guidelines,症状发作后的时间 STEMI
3、危险分层 溶栓风险 转运至熟练PCI导管室所需时间,Circulation 2007 August 10;114:671-719,步骤1：评估时间和危险性,评估STEMI再灌注方式 ACC/AHA 2007 STEMI Guidelines,步骤2：决定应首选溶栓还是PCI 如果时间少于3小时，且介入治疗无耽搁，溶栓和PCI首选哪种都可以，二者在减少梗死面积，降低死亡率方面效果相似。但倾向PCI，因可降低出血与卒中。,Circulation 2007 August 10;114:671-719,312小时患者，PCI可挽救更多心肌，还可减少卒中。如无PCI条件，且有溶栓禁忌，应立即转院。23个
4、随机研究，直接PCI降低全因死亡，非致死MI，卒中，通畅率，心功能等指标优于静脉溶栓。,Circulation 2007 August 10;114:671-719,直接PCI与溶栓疗法的汇萃分析（23个随机研究）,PCI,Lytics,7%,7%,5%,9%,总死亡(包括心源性休克),1%,P=0.0002,P=0.0003,(n=7739),(%)Events,死亡(排除心源性休克),非致命性再次心梗,中风,Hemorrhagic CVA,0.05%,2%,1%,7%,3%,P0.0001,P0.0001,P0.0001,Keeley et al，Lancet 2003;361:13-20
5、,ACC/AHA 2007&ESC 2008 指南:直接PCI 应用于急性ST段抬高心梗,Class I 一般考虑发病 12 小时之内患者就诊到球囊开通血管时间 75 例/年导管室手术量 200 例/年，直接PCI 36 例/年有胸外科支持,Circulation 2007 August 10;114:671-719,Class I 症状发作时间 1小时,溶栓疗法更好 症状发作时间 3小时，直接 PCI 更好,Circulation 2007 August 10;114:671-719,STEMI：直接 PCI 治疗,四个高危亚组直接PCI疗效优于溶栓组心源性休克前壁心梗、再发心梗心力衰竭老年
6、人 70 岁,溶栓治疗是否已经过时？,各种原因导致的时间延迟大大降低了直接PCI的获益。对于不能直接PCI达到理想再灌注的患者，溶栓治疗仍然是较好的选择！即使在欧美国家，AMI再灌注治疗中溶栓与直接PCI的比例相当。国际上多项注册研究显示，虽然PCI治疗近年来增长迅速，但仍有接近40%的患者接受溶栓治疗。,急性ST段抬高心肌梗死溶栓治疗的中国专家共识(2009年更新版).,“时间就是心肌”-时间与死亡率关系（NRMI-2 研究）,P=0.01,P=0.0007,P=0.0003,NRMI 2:Primary PCI door-to-balloon time vs mortality,n=2,2
7、30,5,734,Door-to-balloon time(minutes),6,616,4,461,2,627,5,412,0-60 61-90 91-120 121-150 150-180 180,Mortality(%),不具备24h急诊PCI治疗条件的医院。不具备24h急诊PCI治疗条件也不具备迅速转运条件的医院。具备24h急诊PCI治疗条件，患者就诊早（症状持续3h）；具备24h急诊PCI治疗条件，患者就诊时症状持续大于3小时，但就诊-球囊扩张与就诊-溶栓时间相差（PCI相关的延误）超过60min或就诊-球囊扩张时间超过90min（新指南的建议为：FMC（首次医疗接触）到球囊扩张的时
8、间）。,时间就是心肌！,溶栓治疗首选条件(2009),2009急性ST段抬高心梗溶栓治疗中国专家共识,再次溶栓治疗,如果患者有证据显示血管持续闭塞、开通后在闭塞或下降的ST段再次抬高。患者应该立即进行PCI或转运至可行PCI的医院，此外，可考虑进行再次溶栓治疗，并选择无免疫原性的溶栓药物。,溶栓药物的选择,非特异性纤溶酶原激活剂-链激酶(SK)和尿激酶（UK）特异性纤溶酶原激活剂-人重组组织型纤溶酶原激活剂（rt-PA）瑞替普酶(r-PA)，兰替普酶(n-PA)，替耐普酶(TNK-tPA),不同溶栓药物主要特点的比较,2009急性ST段抬高心梗溶栓治疗的中国专家共识,我国溶栓治疗的患者中绝大多
9、数（90%）应用非选择性溶栓药物,应用组织型纤溶酶原激活剂（t-PA）者仅占2.7%。应该积极推进规范的溶栓治疗，以提高我国急性急性ST段抬高心梗的再灌注治疗的比例和成功率！,急性ST段抬高心肌梗死溶栓治疗的中国专家共识(2009年更新版).,首诊到基层医院的AMI病人，应采取何种再灌注策略：就地溶栓治疗？转运直接 PCI？,PRAGUE 研究,p=ns,p 0.02,Widimsky et al Eur Heart J 2003;24:94,转运PCI 和就地溶栓治疗对死亡率的影响（发病时间考虑）,STEMI：转院距离短，延迟时间不长（PCI90min）,PRAGUE-2 Study(N=3
10、00),p0.001,23.0%,15.0%,8.0%,p0.001,ESC 2007,Sept 1-4,STEMI：拟转院PCI，但延迟时间较长(PCI90min),直接PCI？易化PCI？,ASSENT-4研究,2006年发表在Lancet；1120例患者比较：直接PCI vs 易化PCI；易化PCI组死亡率显著增高；只有低出血/高危STEMI患者获益。,FINESSE研究,2007年ESC会议上公布；2453例STEMI：瑞替普酶+阿昔单抗易化PCI vs 阿昔单抗易化PCI vs 直接PCI虽然易化PCI组术前冠脉血流明显优于直接PCI组，但三组90天死亡、心衰、心源性休克等MACE发
11、生率无差异；易化PCI组出血危险明显增高。,ESC 2007,Sept 1-4,AHA/ACC 2007&ESC 2008 Guideline：异化PCI,低出血风险的高危STEMI患者，在不能立即行PCI时可采用异化PCI策略。（Class b）,2009年：CAPTIM最新随访结果,Bonnefoy E et al,European Heart Journal 2009.,急性ST段抬高心梗患者,直接行PCI(n=421),rt-PA异化PCI(n=419),CAPTIM:异化PCI降低5年全因死亡率,患者症状发作6小时内，rt-PA溶栓后行PCI的5年全因死亡率为 9.7%vs 12.6
12、%,Bonnefoy E et al,European Heart Journal 2009.,症状发作2小时内，p=0.04HR 0.50(95%CI,0.25-0.97),症状发作2小时内，rt-PA溶栓后行PCI的5年死亡率仅为单纯PCI组的50%,Bonnefoy E et al,European Heart Journal 2009.,死亡风险50%,CAPTIM:异化PCI降低5年全因死亡率,2009ESC：NORDISTEMI,Objective:To compare 2 different strategies after thrombolysis for STEMI in p
13、atients with very long transfer times:A:Immediate transfer for CAG/PCIB:Conservative,ischemia-guided treatment,Halvorsen S:Presented in ESC 2009,NORDISTEMI：study design,Bonnefoy E et al,European Heart Journal 2009.,Acute STEMI 90 min,Clinical Outcome at 30 days:,Conservative,Invasive,21%,4.5%,9.8%,1
14、0%,Death,re-MI,strokeNew ischemia,RR=0.49(0.27-0.89)P=0.003,(%)Events,Death,re-MI,stroke),Death,2.2%,2.3%,Bonnefoy E et al,European Heart Journal 2009.,RR=0.45(0.16-1.14)P=0.14,STEMI药物再灌注治疗组成要素,FibrinolyticSKFibrin-specific,AntiplateletASAGP IIb/IIIa Clopidegrel,AnticoagulantUFH Alternative Agents,S
15、TEMI长期双重抗血小板治疗明显获益,CLARITY TIMI-28,COMMIT/CCS-2,ESC 2008:STEMI Guideline,糖蛋白b/a抑制剂：,糖蛋白b/a抑制剂与溶栓药物联合可提高疗效，但出血并发症增加。阿昔单抗和半量瑞替普酶或替奈普酶联合使用进行再灌注治疗对前壁心肌梗死、年龄75岁，没有出血危险因素的患者可能有益，可预防再梗死以及STEMI的并发症。但是临床研究显示，糖蛋白b/a抑制剂与溶栓联合没有降低病死率，尤其对75岁以上的患者，因为出血风险明显增加，不建议药物溶栓与糖蛋白b/a 抑制剂联合。,ESC 2008:STEMI Guideline2009STEMI溶
16、栓治疗的中国专家共识,依诺肝素显著降低主要终点事件（死亡或非致命性心梗）相对风险17(ExTRACT-TIMI 25),相对风险:0.83(0.770.90)p0.0001,依诺肝素,普通肝素,0,5,10,15,20,25,30,天,0,3,6,9,12,15,主要终点事件(%),相对风险:0.90(0.801.01)p=0.08,相对风险:0.77(0.71 0.85)p0.0001,48 h,8 days,9.9%,12.0%,4.7%,5.2%,7.2%,9.3%,RRR17%,2,8,(2006年3月ACC 上首次公布的对所有患者的分析结果),Thank you for your a
17、ttention!,Thrombolysis and antithrombolism for STEMI-Advancement in 2009,Zuyi YuanDept of Cardiovascular Medicine,First Affiliated Hospital of Medical School,Xian Jiaotong University,Goals for AMI Therapy,Restore coronary blood flow to ischemic myocardiumRapidly,Completely and sustain,Reducing the m
18、ortalityAMI survivor with an improved outcome,Yusuf S,et al.Circulation.1990;82(suppl II):II-117-II-134.Schrder R,et al.J Am Coll Cardiol.1995;26:1657-1664.,Time is the Myocardium！Time is the life！,Symptom Recognition,Call to Medical System,ED,Cath Lab,PreHospital,Delay in Initiation of Reperfusion
19、Therapy,Increasing Loss of Myocytes,Treatment Delayed is Treatment Denied,Thrombolysis？Primary PCI？,STEMI:the choice of strategies for reperfusion,Thrombolysis vs Primary PCI,ThrombolysisTIMI 3 flow:60%Re-MI rate:4%Stroke rate:2%ICH rate:1%Anywhere(pre-hospital)anytimeAll doctorNo time delayRCT docu
20、mented,Primary PCITIMI 3 flow:80-90%Re-MI rate:1h),Strategies for STEMI:ACC/AHA 2007&ESC 2008 STEMI Guidelines,the time of onset present STEMI risk score risk of thrombolysis the time for transfer to PCI cathlab,Circulation 2007 August 10;114:671-719,Step 1：Evaluating the time and risk,Step 2：The ch
21、oice of thrombolysis or PCI?If the time of onset is 3 hours,and no invasive delay,no difference in thrombolysis and PCI;the two strategies are similar in reducing the area of infarction and reducing mortality.But prefer to PCI,since to reducing bleeding and stroke.,Circulation 2007 August 10;114:671
22、-719,Strategies for STEMI:ACC/AHA 2007&ESC 2008 STEMI Guidelines,Onset in 312 hours,PCI is the better,because of salvaging more ischemic myocardium,and reducing the stroke.If no PCI qualification,and have the counterconditions，the patient should be transfer immediately.23 RCT have documented,primary
23、 PCI reduce the mortality,re-MI,stroke,and preserved the heart function is better vs thrombolysis.,Circulation 2007 August 10;114:671-719,Primary PCI vs Thrombolysis:Meta-analysis（23 RCT）,PCI,Lytics,7%,7%,5%,9%,Total mortality,1%,P=0.0002,P=0.0003,(n=7739),(%)Events,mortality,Re-MI,stroke,Hemorrhagi
24、c CVA,0.05%,2%,1%,7%,3%,P0.0001,P0.0001,P0.0001,Keeley et al，Lancet 2003;361:13-20,ACC/AHA 2007&ESC 2008 Guigeline:Primary PCI in STEMI:,Class I In generalOnset 75 case/yearCathlab PCI case 200 case/year,Primary PCI 36 case/yearSurgical standby,Circulation 2007 August 10;114:671-719,Class I if onset
25、 1 hour,thrombolysis is better if onset 3 hours，primary PCI is better,Circulation 2007 August 10;114:671-719,STEMI：Primary PCI,Four high risk score subgroup the PCI is better vs thrombolysisCardiac shockAnterioreor M,re-MIHeart failureage 70 years,Thrombolytic therapy is behind the times？,Different
26、causes result in PCI time delay limited the primary PCI benefice.For nor primary PCI usable patients,thrombolysis is still the best chioce！Although in western，AMI reperfusion therapy is still important.International register study showed:40%AMI were performed thrombolysis.,急性ST段抬高心肌梗死溶栓治疗的中国专家共识(200
27、9年更新版).,“Time is the myocardium”the ralationship of Time and Mortality（NRMI-2 study）,P=0.01,P=0.0007,P=0.0003,NRMI 2:Primary PCI door-to-balloon time vs mortality,n=2,230,5,734,Door-to-balloon time(minutes),6,616,4,461,2,627,5,412,0-60 61-90 91-120 121-150 150-180 180,Mortality(%),For hospital:No 24
28、h primary PCI cathlab usable。For hospital:No 24h primary PCI cathlab usable,and meantime,thansfer is delay.For hospital:24h primary PCI cathlab usable，onset 3 hours；D-B time D-N time 60min。,Time is the myocardium！,First Chioce for Thrombolysis(2009),2009急性ST段抬高心梗溶栓治疗中国专家共识,Re-thrombolytic therapy:,I
29、f have evidence showed the failure of reperfusion and re-MI,patient should be transfer to perform PCI immediately,otherwise patient should be perform re-thrombolytic therapy.,The Chioce of Thrombolytic Drugs,非特异性纤溶酶原激活剂-链激酶(SK)和尿激酶（UK）特异性纤溶酶原激活剂-人重组组织型纤溶酶原激活剂（rt-PA）瑞替普酶(r-PA)，兰替普酶(n-PA)，替耐普酶(TNK-tPA
30、),The characteristic comparion of difference thrombolytic drugs,2009急性ST段抬高心梗溶栓治疗的中国专家共识,我国溶栓治疗的患者中绝大多数（90%）应用非选择性溶栓药物,应用组织型纤溶酶原激活剂（t-PA）者仅占2.7%。应该积极推进规范的溶栓治疗，以提高我国急性急性ST段抬高心梗的再灌注治疗的比例和成功率！,急性ST段抬高心肌梗死溶栓治疗的中国专家共识(2009年更新版).,For AMI patient,the first contact in raral hospital，which strategies for rep
31、erfusion：Thrombolysis？Transfer to PCI？,PRAGUE study,p=ns,p 0.02,Widimsky et al Eur Heart J 2003;24:94,Transfer PCI vs Thrombolysis（onset time concise）,STEMI：short transfer distant，no cathlab delay（PCI90min）,PRAGUE-2 Study(N=300),p0.001,23.0%,15.0%,8.0%,p0.001,ESC 2007,Sept 1-4,STEMI：is plan to PCI，b
32、ut cathlab delay(PCI90min),Primary PCI？After thrombolytic PCI(TT-PCI)？,ASSENT-4 study,2006 published in Lancet；1120 case：Primary PCI vs TT-PCI；The mortality is significant higher in TT-PCI group；Only the low bleeding/high risk STEMI subgroup is beneficial。,FINESSE study,First presented in ESC 2007；2
33、453 case STEMI：rt-PA+GPI PCI vs GPI PCI vs Primary PCIAlthough the cronary flow is better in TT-PCI compare the preimary PCI,but the three groups have not difference in death,HF,cardiac shock(MACE)；The risk for bleeding is high in TT-PCI group.,ESC 2007,Sept 1-4,AHA/ACC 2007&ESC 2008 Guideline：for T
34、T-PCI,Low bleeding risk and high risk score STEMI patient，TT-PCI perform in no cathlab usable。（Class b）,2009：CAPTIM new F-U data,Bonnefoy E et al,European Heart Journal 2009.,CAPTIM:TT-PCI reduce the 5-year mortality,Bonnefoy E et al,European Heart Journal 2009.,Onset 2hours，p=0.04HR 0.50(95%CI,0.25
35、-0.97),Bonnefoy E et al,European Heart Journal 2009.,RR50%,CAPTIM:TT-PCI reduce the 5-year mortality,2009ESC：NORDISTEMI,Objective:To compare 2 different strategies after thrombolysis for STEMI in patients with very long transfer times:A:Immediate transfer for CAG/PCIB:Conservative,ischemia-guided tr
36、eatment,Halvorsen S:Presented in ESC 2009,NORDISTEMI：study design,Bonnefoy E et al,European Heart Journal 2009.,Acute STEMI 90 min,Clinical Outcome at 30 days:,Conservative,Invasive,21%,4.5%,9.8%,10%,Death,re-MI,strokeNew ischemia,RR=0.49(0.27-0.89)P=0.003,(%)Events,Death,re-MI,stroke),Death,2.2%,2.
37、3%,Bonnefoy E et al,European Heart Journal 2009.,RR=0.45(0.16-1.14)P=0.14,STEMI:Drug reperfusion,FibrinolyticSKFibrin-specific,AntiplateletASAGP IIb/IIIa Clopidegrel,AnticoagulantUFH Alternative Agents,STEMI长期双重抗血小板治疗明显获益,CLARITY TIMI-28,COMMIT/CCS-2,ESC 2008:STEMI Guideline,GPb/a inhibitors：,GPb/a
38、inhibitor conbam thrombolysis,the therapeutics is increase，but the bleeding is also increase。GPI conbam half-dose rt-PA usage in anterior MI,age75 years,no bleed risk group is beneficial，can prevent the corbility of STEMI。But PCT showed，GPb/a inhibitor conbam thrombolysis can not reduce the mortalit
39、y,because the increasing bleeding.,ESC 2008:STEMI Guideline2009STEMI溶栓治疗的中国专家共识,ExTRACT-TIMI 25:Enoxaparin on AMI,RR:0.83(0.770.90)p0.0001,enoxaparin,haprin,0,5,10,15,20,25,30,天,0,3,6,9,12,15,MACE(%),RR:0.90(0.801.01)p=0.08,RR:0.77(0.71 0.85)p0.0001,48 h,8 days,9.9%,12.0%,4.7%,5.2%,7.2%,9.3%,RRR17%,2,8,Thank you for your attention!,
