STEMI血运重建治疗原则与流程 北京大学第一医院心内科 李建平

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1 STEMI血运重建治疗原则与流程 北京大学第一医院心内科 李建平

2 背 景 冠心病是目前世界范围内致死与致残的主要原因之一。 在美国，每年约有900万人发生心肌梗死。
社区人群：发病后第一个月死亡率甚至高达50%，其中半数死于发病后2小时内。 住院患者： 未接受再灌注治疗死亡率约15%；接受再灌注治疗死亡率4—6% 我国：每年新发心肌梗死至少50万，现患心肌梗死至少200万人。2007年冠心病死亡粗率为45-65/10万人。 European Heart Journal 2008;29: 中国心血管病报告

3 时间就是心肌，就是生命 时间对再灌注抢救的意义 0 - 0.5 hrs 预防梗死 0.5 – 2 hrs 大量挽救心肌 + IRA开通的益处

4 STEMI患者首要的治疗是心肌再灌注 溶栓 S T PCI E M 急诊CABG I 尽早、充分、持续 实现心肌再灌注
最大限度地挽救频死心肌 保护心脏功能 溶栓 PCI 急诊CABG S T E M I

5 90年代中期已证明溶栓治疗的益处 与安慰剂对比

6 STEMI直接PCI vs 溶栓 (23 RCTs, N=7739)
25 短期疗效 (4–6 周) PCI Thrombolytic therapy P<.0001 20 P<.0001 15 频率, % P=.0002 P<.0001 P=.032 10 5 P<.0001 This meta-analysis encompassed 23 trials in which 3872 patients with STEMI were randomized to primary percutaneous transluminal coronary angioplasty (PTCA) and 3867 patients were randomized to thrombolytic therapy. Stents were used in 12 of the 23 trials and in 8 trials GP IIb/IIIa inhibitors were used. Results indicated that the incidence of every short-term clinical outcome of interest was significantly higher in patients receiving thrombolytic agents than it was in those who underwent primary PTCA. Results with PTCA continued to be superior to those with thrombolysis during long-term follow-up and were independent of the type of thrombolytic agent used (76% received a fibrin-specific agent rather than streptokinase) and whether or not the patient was transferred to primary PTCA. 死亡 非致死 心梗 再发缺血 出血性 卒中 主要 出血 死亡、 再梗 或卒中 Keeley EC, et al. Lancet. 2003;361:13. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet. 2003;361:13-20. 6

7 美国STEMI再灌注治疗状况 STEMI Reperfusion Not Eligible for Reperfusion Therapy
Contraindication Listed N= 3,514 (17%) No Reperfusion – No Contraindication Listed N = 880 (4%) Primary PCI – 85%* Fibrinolytics – 9%* Both PCI + Lytics – 6%* >90% of eligible patients reperfused >90% utilized PCI ACTION Registry-GWTG DATA: July 1, 2007 – June 30, 2008 * Among patients receiving reperfusion

8 欧洲住院STEMI再灌注治疗状况 Widimsky P et al. Eur Heart J 2010;31:943-957
Hospitalized STEMI treatment in Europe (data from national registries or surveys). 100%, all hospitalized STEMI patients in each given country; green colour, STEMI patients treated by primary PCI; red colour, STEMI patients treated by thrombolysis; black colour, STEMI patients not treated with any reperfusion. Countries abbreviations: CZ, Czech Republic; SLO, Slovenia; DE, Germany; CH, Switzerland; PL, Poland; HR, Croatia; SE, Sweden; HU, Hungary; BE, Belgium; IL, Israel; IT, Italy; FIN, Finland; AT, Austria; FR, France; SK, Slovakia; LAT, Latvia; UK, United Kingdom; BG, Bulgaria; PO, Portugal; SRB, Serbia; GR, Greece; TR, Turkey; RO, Romania. Widimsky P et al. Eur Heart J 2010;31:

9 我国STEMI再灌注治疗状况 北京市STEMI急诊救治现状的多中心注册研究： 北京地区急性心肌梗死患者接受再灌注治疗比例为80.9％
其中15.4％接受了溶栓治疗，65.5％接受了急诊介入治疗 平均开始溶栓时间(Door-to-needle, D2N)为83分钟，入门-球囊时间( Door-to-baloon, D2B )为132分钟。 只有7％接受溶栓患者D2N时间<30分钟，只有22％的患者D2B时间<90分钟

10 美国STEMI患病率与急诊PCI资源 全美只有25%的医院具有行PCI的能力
Yeh RW et al. NEJM 2010;362:2155

11 时间与院内死亡率 Door–to–Balloon Time: NRMI–3/4
7.4 N = 29,222 P < 0.001 5.7 4.2 3.0 McNamara RL, et al. JACC. 2006;47:2180.

12 STEMI治疗目标与挑战 目标：IRA早期、充分、持续地开通 挑战：时间、资源、地域分布 解决途径：加强培训 急诊救治体系（绿色通道）的构建

13 工作时间与非工作时间对STEMI患者PCI的影响 Zwolle Group: 1,702 STEMI pts 1994 – 2000
8 失败 PCI 6.9 Percent 死亡率, 30-day 6 P < 0.01 4.2 3.8 4 P < 0.01 1.9 2 Successful PCI = T3 flow and less than 50% stenosis 入院时间: 0800 – 1800 h 1800 – 0800 h Henriques JPS, et al. J Am Coll Cardiol. 2003;41:2138. 13

14 术者经验对死亡率的影响: NRMI Hospital Mortality (%) <16 16-48 >48 术者年手术量
9 6.2 5.9 5.9 6 5.4 Lytic 4.5 3.4 PCI 3 <16 16-48 >48 术者年手术量 Magid DJ, et al. JAMA. 2000;284:3131.

15 可以从事直接PCI的医院的任务 加强培训 确保24小时随叫随到的介入治疗医护技团队
完善院内绿色通道，尽可能缩短 Door to Balloon时间

16 不能行急诊PCI的医院，怎么办？

17 PCI与溶栓获益大小的影响因素- 症状开始至接受治疗时间
PRAGUE–2 CAPTIM 10 20 15.3 5.9 5.7 死亡率 (%) 5 10 3.7 7.4 7.3 6 2.2 < 2 h > 2 h < 3 h > 3 h 溶栓 PCI Bonnefoy E, et al. Lancet. 2002;360:825. Widimsky P, et al. Eur Heart J. 2003;24:94.

18 25% of patients high risk (TIMI ≥ 5)
PCI与溶栓获益大小的影响因素- 病人危险性: DANAMI-2 40 – 30 – 20 – 10 – 0 – 25% of patients high risk (TIMI ≥ 5) TRS ≥ 5 P = 0.02 Mortality (%) Fibrinolysis PCI TRS 0 – 4 P = 0.11 | | | | Years Thune JJ, et al. Circulation 2005;112:2017. 18

19 溶栓还是转运PCI？ PCI导致的时间延迟是决定死亡率的关键因素
pts at 645 NRMI hospitals Pinto et al. Circulation. 2006;114:

20 其它的解决途径？挽救性 PCI 先溶栓 60-90分钟后判断溶栓是否成功 溶栓失败转运行挽救性 PCI Baseline
90 min later

21 挽救性PCI：REACT研究结果 P < 0.01 % pts 主要终点：6个月时死亡、心梗、严重心衰 再次溶栓 保守治疗
Gershlick N EJM 2005;353:

22 2007 STEMI Focused Recommendation: Rescue PCI
Class IIa indication: 存在持续的缺血症状 溶栓90分钟后ST段抬高最明显的导联ST段 恢复不足50%，中-大面积心肌处于缺血危险 references 22

23 易化 PCI 在决定实施直接PCI后，首先给予一个药物治疗如全量的溶栓剂、半量的溶栓药、GPIIb/IIIa受体拮抗剂、或者减量的溶栓药物与GPIIb/IIIa受体拮抗剂的联合应用

24 ASSENT 4 研究 *Primary endpoint: death, CHF, or
shock within 90 days of randomization Lancet, 2006;367:

25

26 2007 STEMI Focused Recommendation: 易化 PCI
Class IIb: 等级C 非全量溶栓剂的易化PCI只有在满足以下全部临床状况 下可以考虑使用： a、高危 b、PCI不能在90分钟之内进行 c、出血风险低 Class III：等级B 全量溶栓剂的易化PCI

27 GP IIb IIIa Inhibitors in STEMI
Class IIa It is reasonable to start treatment with abciximab as early as possible before primary PCI (with or without stenting) in pts with STEMI. (Level of Evidence: B) Class IIb Treatment with tirofiban or eptifibatide may be considered before primary PCI (with or without stenting) in patients with STEMI. (LOE: C) Expect changes with next guidelines ACC/AHA 2004 Guidelines JACC 2004;44;E211

28 FINESSE* Trial Design Primary Endpoint: Death, V-Fib > 48 hrs, shock or CHF requiring re-hospitalization at 90 days *The Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events (FINESSE) study Ellis SG et al. N Engl J Med 2008;358:

29 Pts with Primary Endpoint*
FINESSE: KM Curves for Pts with Primary Endpoint* *Primary endpoint: death from all causes, V Fib > 48 hrs after randomization, cardiogenic shock, or CHF requiring rehosp. or ER visit, through 90 days As compared with abciximab given at the time of PCI, neither facilitation of PCI with reteplase plus abciximab nor facilitation with abciximab alone significantly improved clinical outcomes. Ellis SG et al. N Engl J Med 2008;358:

30 Primary Endpoint Components (30 days)
ADMIRAL Primary Endpoint Components (30 days) % p = 0.02 % p = 0.33 % p = 0.65 % p = 0.02

31 Clopidogrel Pretreatment in Primary PCI: Pooled Analysis of 26 Trials
OR (95% CI) P Value TIMI Grade 2/3 Flow 1.51 ( ) <0.0001 1.53 ( ) Mortality 0.57 ( ) 0.0055 0.52 ( ) Death/Re-MI 0.54 ( ) 0.0003 0.50 ( ) Multivariate-adjusted treatment effect (age, gender, DM, HBP, heparin dose, symptom duration, smoking, yr publication) Propensity score-adjusted treatment effect 300mg in 25 trials and 600mg in 1 trial Vlaar et al. Circ 2008;118:1828

32 GP IIb/IIIa before PCI in pts Pretreated with 600 mg Clopidogrel
Tirofiban Eptifibatide Abciximab Mehilli J. Circulation 2009;119: Le May M. Circ CV Intervention 2009 in press A W J van‘t Hof Lancet 2008; 372: 537–46

33 TIMI Flow Pre PCI Brave-3 On-TIME 2 ASSIST

34 GP IIb/IIIa before PCI in pts Pretreated with 600 mg Clopidogrel
Death ReMI Death / ReMI / CVA p=0.14 p=0.87 p=0.46 p=0.48 p=0.54 p=0.62 n=950 n=800 n=400 Lecture Notes On-TIME 2 BRAVE-3 ASSIST AWJ van‘t Hof et al. Lancet 2008;372: J Mehilli et al. ACC 2008 M Le May et al. TCT 2008 34

35 TIMI Bleeding Events During Initial Hospitalization
% pts p = 0.14 p = 0. 21 p = 0.04

36 药物-介入 病人接受溶栓治疗（或联合GP IIb/IIIa受体拮抗剂）作为初始的再灌注治疗 以后尽可能快地被送往可以行PCI的医院

37 TRANSFER AMI Community Hospital Emergency Department PCI Centre
High Risk STEMI  12 hrs TNK + ASA + Clopidogrel + Heparin or Enoxaparin Randomization Pharmacoinvasive Strategy: Urgent Transfer to PCI Centre Standard Treatment Strategy: Assess chest pain, ST resolution at min after randomization PCI Centre Failed Reperfusion* Successful Reperfusion Cath / PCI within 6 hrs regardless of reperfusion status Cath and Rescue PCI  GP IIb/IIIa Inhibitor Elective Cath  PCI > 24 hrs later * ST segment resolution < 50% & persistent chest pain, or hemodynamic instability Cantor WJ et al. N Engl J Med 2009;360:

38 TRANSFER AMI研究 主要终点：30天时死亡、再梗、再发缺血、新发或恶化的心衰或心源性休克
Cantor WJ et al. N Engl J Med 2009;360:

39 TRANSFER AMI研究：30天时事件发生率
% pts p = 0.004 p = 0.06 p = 0.04 p = 0.39 p = 0.003 p = 0.23 Re-MI New or Worse CHF Composite

40 STEMI患者直接PCI推荐指征

41 2009 STEMI溶栓治疗专家共识

42 Bradley EH et al. NEJM 2006;355:2308

43 急诊介入治疗时间段分析 31 30 24 D-B Door-Balloon时间：平均85分钟 由3部分时间组成，即 就诊到病人同意治疗时间
病人同意治疗到进导管室时间 入导管室至球囊扩张时间： 31 30 24 D-B

44 影响血运重建的相关因素分析 患者就诊的医疗机构—--大的医疗中心，还是基层医院或社区医疗机构 发病到就诊的时间 患者的经济条件及文化背景
导管室开放状态 介入治疗队伍

45 如何缩短AMI发病至血运重建的时间？以提高AMI救治水平(1)
加大宣传力度，动员社会力量，倡导有胸痛到医院、找医生的理念 建立社区急性心肌梗死救治绿色通道 建立院内急性心肌梗死热线，或急性胸痛热线

46 如何缩短AMI发病至血运重建的时间？以提高AMI救治水平(2)
有条件的医院建立胸痛门诊，或成立胸痛中心，建立或完善胸痛的诊治流程 建立完善急诊医疗保障系统 导管室24小时全天候开放 成立急诊介入治疗小组

47 建立胸痛中心 “胸痛中心”是为降低急性心肌梗死的发病率和死亡率提出的概念，通过多学科（包括急救医疗系统（EMS）、急诊科、心内科、影像学科）合作，提供快速而准确的诊断、危险评估和恰当的治疗手段，对胸痛患者进行有效的分类治疗，从而提高早期诊断和治疗ACS的能力，降低心肌梗死发生的可能性或者避免心肌梗死发生，并准确筛查出心肌缺血低危患者，达到减少误诊和漏诊及过度治疗，以及改善患者临床预后的目的。 中华医学会心血管病学分会：《“胸痛中心”建设中国专家共识》

48 ＞12小时STEMI的特点 以高龄患者为多； 多合并其它疾病（糖尿病、高血压、慢性肾病、脑血管疾病、肿瘤等）； 更倾向于保守治疗；
当地医疗条件相对不足，依从性差； Background— Treatment with lytics or primary percutaneous coronary interventions (PCI) reduces the mortality rate of patients with ST-elevation myocardial infarction (STEMI) presenting within 12 hours. Patients presenting >12 hours are generally considered to be ineligible for reperfusion therapy, and there are currently no specific treatment recommendations for this subgroup. Methods— All patients with STEMI <24 hours were included in the Treatment with Enoxaparin and Tirofiban in Acute Myocardial Infarction (TETAMI) randomized trial or registry. Those patients who were ineligible for acute reperfusion, had no cardiogenic shock, and were not planned for revascularization within 48 hours were randomized to 1 of 4 antithrombotic regimens involving enoxaparin or unfractionated heparin (UFH), in combination with tirofiban or placebo for 2 to 8 days. A concurrent registry tracked STEMI patients coming in within <12 hours, and who underwent reperfusion. This registry also tracked the remaining STEMI patients who neither received reperfusion nor were enrolled in the TETAMI randomized trial. The demographics and clinical outcomes of all three groups (received reperfusion therapy, too late for reperfusion and enrolled in the randomized trial, neither received reperfusion therapy nor were enrolled in the randomized trial) were prospectively tracked. Results and Conclusion— There were 2,737 patients who presented with STEMI or a new left branch bundle block (LBBB), of which 1,654 (60%) presented 12 hours. There were 1,196 (72%) of 1,654 patients who received reperfusion therapy. There were 458 (28%) of the 1,654 patients deemed "ineligible" for reperfusion, mostly because of a contraindication to lytics or for being "too old." In contrast, 1,083 (40%) of 2,737 patients presented >12 hours. Apart from 34 of these patients who had a stuttering infarction and were referred for reperfusion, the remaining patients did not receive reperfusion therapy. Registry patients who received reperfusion therapy, compared with TETAMI randomized patients (all of whom received antithrombotic therapy) and registry patients who did not receive reperfusion, were younger (61 years versus 63 years and 67 years), were more likely to be male (78% versus 73% and 63%), and had persistent ST-segment elevation as opposed to LBBB or Q waves. Registry patients who received reperfusion therapy had better clinical outcomes, even after adjusting for admission Killip class, compared with TETAMI randomized patients and registry patients who did not receive reperfusion therapy. TETAMI randomized patients had better outcomes than registry patients who did not receive reperfusion therapy. The major obstacle to expanding the delivery of reperfusion therapy to patients with STEMI is the large fraction of patients who present too late for reperfusion therapy. Examination of prospectively gathered data on STEMI patients who are ineligible for reperfusion may help optimize their treatment. Data from TETAMI Study Circulation. 2003;108:III-14-III-21 48

49 ＞12小时STEMI的指南建议 临床表现 ESC 2008 ACC/AHA/SCAI 2009 ＞12小时就诊，同时伴有： 再发心梗 N/A
急诊PCI (I, C) 心源性休克 or 血流动力学不稳定 急症PCI (I, C) 急诊PCI (I, B) 恶性心律失常 or 心衰 急诊PCI (IIa, C) ＞12小时就诊，同时伴有持续性心绞痛 12-24小时就诊，无症状 急诊PCI (IIb, B) ＞24小时就诊，无症状 不推荐急诊PCI (III, B) 49

50 2010 ESC PCI GUIDELINE

51 谢谢