AMI再灌注治疗， 院前我们能做什么 张斌 广东省人民医院 广东省心血管病研究所

Presentation on theme: "AMI再灌注治疗， 院前我们能做什么 张斌 广东省人民医院 广东省心血管病研究所"— Presentation transcript:

1 AMI再灌注治疗， 院前我们能做什么 张斌 广东省人民医院 广东省心血管病研究所
有诸多因素造成急性心肌梗死患者就诊延迟，导致患者死亡率增加。作为胡大一教授领衔的北京市科委重大课题的分课题，我们对2006年在首都医科大学附属北京安贞医院心肺血管疾病抢救中心就诊的前200例急性ST抬高心肌梗死患者进行了问卷调查，结果如下：  一、院前因素       1．患者本身因素       （1）医疗保险：享有社会医疗保险或公费医疗者，往往较自费患者就诊时间短。       （2）受教育程度：患者受教育程度越高，就诊时间往往较短。我们统计，具有高中以上文化程度的患者就诊时间往往相应更短。       （３）是否工作：患者是否工作与就诊时间并无明显差别。       （４）职业：患者的职业与就诊时间并无明显差别。       （５）婚姻状况：患者的婚姻状况与就诊时间并无明显差别。       （６）收入状况；高收入患者较低收入患者就诊时间往往相应较短。我们统计，月收入在2000元以上的患者就诊时间往往相应更短。       （７）居住状况：患者的居住状况与就诊时间并无明显差别。       （８）长期居住在北京（以6个月为界限）：长期居住在北京患者的就诊时间往往相应较短。       （９）症状：既有类似症状的患者就诊时间往往相应较短。症状较重的患者就诊时间往往相应较短。       ２．就诊途径       就诊途径包括拨打999或120急救电话就诊、自行开车或坐出租车或步行就诊和通过其他医院转诊三种方式。其中直接拨打急救电话的患者就诊时间往往相应较短。       ３．发病地点       发病地点包括家中、工作中和路上三种情况。相比较而言在家中的患者就诊时间往往相应较短。       ４．发病时间       从发病时间上来看早5点至晚10点发病的患者就诊时间往往相应较短，夜间入睡后患者的就诊时间会被延迟。        5.   旁观者情况       有旁观者比没有旁观者患者就诊时间往往相应较短。旁观者受教育程度越高（以高中以上学历）患者就诊时间往往相应较短。 旁观者以往曾有类似经历或见过急性心肌梗死患者，患者就诊时间往往相应较短

2 DOOR NEEDLE BALLOON

3 时间就是心肌！ 在TCT2007会议上，Harbor-UCLA医学中心的WiliamJ. French 博士介绍说，在过去的12年里，美国无需转运的STEMI患者接受介入检查治疗的Door-to-Ballon时间逐年减少，目前约有65%的患者能够在90min内得到有效的介入治疗，而以往这一比例仅为34%。美国AHA所倡导的“我们的使命-患者的生命”（Mission:Lifeline）活动和全美范围内各医院积极行动是将Door-to-Ballon时间减少到90min内的重要原因。另一项重要的改变在于转运患者的时间得到了有效的控制， WiliamJ. French 博士介绍说，患者症状出现到医院就诊（symptom onset-door）时间从2001年的1.75hr，减少到2006年的1.4hr。此外，患者就诊后得到更有效治疗的比例进一步提高，有研究显示，在最近5年里，经脉溶栓的比例已经降至15%，而急诊PCI的比例已升至65%，对于无需转运的STEMI患者，在一些医院其Door-to-Ballon时间已从1994年的80min减少到2006年的50min。从患者出现症状到导管室接受介入治疗的时间也进一步缩短，从1994年的6.9hr减少到2006年的4.3小时，而对于无需转运的患者，这一时间由4hr缩短为3.2hr，相应的这一变化直接导致了院内死亡率的降低，从1990年的9.7%下降到2004年的4.2%，对于无需转运的患者这一比例由5.3%降低到4.2%

4 缩短时间

5

6 Prompt reperfusion treatment is essential for patients who have myocardial infarction with ST-segment elevation. Guidelines recommend that the interval between arrival at the hospital and intracoronary balloon inflation (door-to-balloon time) during primary percutaneous coronary intervention should be 90 minutes or less. However, few hospitals meet this objective. We sought to identify hospital strategies that were significantly associated with a faster door-to-balloon time. METHODS: We surveyed 365 hospitals to determine whether each of 28 specific strategies was in use. We used hierarchical generalized linear models and data on patients from the Centers for Medicare and Medicaid Services to determine the association between hospital strategies and the door-to-balloon time. RESULTS: In multivariate analysis, six strategies were significantly associated with a faster door-to-balloon time. These strategies included having emergency medicine physicians activate the catheterization laboratory (mean reduction in door-to-balloon time, 8.2 minutes), having a single call to a central page operator activate the laboratory (13.8 minutes), having the emergency department activate the catheterization laboratory while the patient is en route to the hospital (15.4 minutes), expecting staff to arrive in the catheterization laboratory within 20 minutes after being paged (vs. >30 minutes) (19.3 minutes), having an attending cardiologist always on site (14.6 minutes), and having staff in the emergency department and the catheterization laboratory use real-time data feedback (8.6 minutes). Despite the effectiveness of these strategies, only a minority of hospitals surveyed were using them. CONCLUSIONS: Several specific hospital strategies are associated with a significant reduction in the door-to-balloon time in the management of myocardial infarction with ST-segment elevation. Copyright 2006 Massachusetts Medical Society

7 2007 TCT:来自St. Francis 心脏中心的UmeshKhot博士介绍了Indianapolis的具体经验。该中心从2005年开始着手制定有效的制度以确保缩短Door-to-Ballon时间，急诊科医生接诊STEMI患者后立即通知导管室医生，由此激活应急系统。为进一步减少时间耽搁，介入医生直接在急诊室或是导管室对患者进行临床评价，患者必须立即由特护人员直接送至已作好接诊准备的导管室。这一制度的实施有效的减少了Door-to-Ballon时间，以前只有28%的患者Door-to-Ballon时间少于90min，而目前这一比例已经升至71% . Massachusetts 心脏中心的Kenneth Rosenfield 博士介绍了Boston的成功作法，该市明确规定转运患者只能在具备急诊PCI条件的医疗中心进行，以避免因在医院间来回转运而浪费宝贵的时间。这一举措有效的减少了相应的时间延误，2006年约有73%的STEMI患者Door-to-Ballon时间小于90min，而在2004年这一比例仅为64%，2006年平均Door-to-Ballon时间为67.5min，2004年为83.5min，2005年为73min。Kenneth Rosenfield 博士认为，之所以能够有如此明显的效果，关键在于全市范围内急救系统与急诊室及导管室之间的积极协作。 Mayo临床中心的Henry H. Ting博士介绍了该中心有效减少Door-to-Ballon时间的方法。该院对于原有的胸痛患者就诊的流程作了修改，省略了由CCU医生评价及转运至CCU观察等步骤，并且将Door to ECG时间由原来的14min缩短到4min。通过这一措施，目前Door to ECG时间已由3年前的90min降低至现在的66min。Henry H. Ting博士介绍说，通常STEMI患者的Door-to-Ballon时间约为66min，夜间或周末时间约为74min，其间的差异主要在于导管室的准备及相关人员的到达时间的不同

8 D2B Times Surpass National Campaign’s Goal
Elizabeth H. Bradley, PhD. Yale School of Public Health. Friday, December 04, 2009 The American College of Cardiology (ACC) Door-to-Balloon (D2B) 联盟目标：STEMI 病人 D2B ≤ 90 minutes 达到 75%. 从2005年4月到 2008年3月，614医院参加NCDR登记研究并加入 D2B 联盟 3年中 82,610 住院患者D2B时间显著缩短 Bradley EH, Nallamothu BK, Herrin J, et al. National efforts to improve door-to-balloon time: Results from the Door-to-Balloon Alliance. J Am Coll Cardiol. 2009;54:2423–2429

9 Table 1. Changes in Use of Recommended Strategies
Strategy 2005 2008 Increase P Value 急诊通知导管室 52.1% 59.7% 7.6% 0.0009 单独呼叫系统激活导管室 30.6% 37.3% 6.7% 0.0012 梯队30分钟内到达导管室 81.2% 88.7% 7.5% < 0.001 即时资料反馈 61.2% 78.6% 17.4% 激活院前 ECG 32.7% 41.1% 8.4% 0.0001

10 Impressive 3-Year Increase
62.8% of US patients had a D2B time within 90 min in 2006 By 2008, the percentage had increased to 76.4%, slightly better than the initial goal of 75% set at the start of the campaign continued to improve beyond the end of the study period (March 31, 2008). 81.7% of eligible patients had D2B times ≤ 90 minutes from June 30, 2009 The average D2B time from an average of 121 minutes at the end of 2005, to an average of 80 minutes as of June 30, 2009

11 Still Room for Improvement
Direct transportation to catheterization laboratory by emergency teams reduces door-to-balloon time Extend accomplishment out into the community so that patients presenting to smaller hospitals and can have faster times from first contact with the health care system until reperfusion 1.Benefit of direct ambulance to coronary care unit admission of acute myocardial infarction patients undergoing primary percutaneous intervention. Amit G, Cafri C, Gilutz H, Ilia R, Zahger D. Department of Cardiology, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. Comment in: Int J Cardiol Jul 31;119(3): BACKGROUND: Early reperfusion therapy in ST-segment elevation myocardial infarction (STEMI) patients improves left ventricular (LV) function and survival. However, emergency room (ER) triage may unnecessarily delay this time-dependent treatment. We sought to determine whether direct admission of STEMI patients from the mobile intensive care units to the intensive coronary care unit (ICCU), bypassing the ER, can shorten the time intervals for primary PCI (PPCI) and improve prognosis. METHODS: All STEMI patients who underwent PPCI between Jan-2002 to Nov-2005 were included. Baseline, clinical and time interval parameters were compared between groups. Mortality rates were obtained through the population register. RESULTS: Of 533 admissions, 115 (21%) were admitted directly to the ICCU. These patients were younger (mean (+S.D.) age of years) than patients admitted via the ER (62+/-13 years, P<0.01) and had a lower proportion of women (9% vs. 22%, P<0.01), hypertension (45% vs. 62%, P<0.01) and diabetes (15% vs. 27%, P=0.01). Directly admitted patients had a substantially shorter median pain-to-balloon time (210 vs. 247 min, P=0.02) as well as s significantly shorter door-to-balloon time (70 vs. 94 min, P<0.01), a difference that was particularly pronounced during daytime (55 min vs. 90 min, P<0.01). There were no significant differences in LV function at 24 h as assessed by echocardiography or infarct size as determined by peak creatine kinase levels. We observed a trend towards reduced 30-day (5.2% vs. 9.8%, P=0.12) and 1-year (11.1% vs. 16.1%, P=0.25) mortality in directly admitted patients. CONCLUSIONS: Directly admitted STEMI patients differ from patients admitted via the ER; Direct ICCU admission, based on a pre-hospital ECG, can substantially shorten time to treatment. 2.Primary percutaneous coronary intervention in acute myocardial infarction: direct transportation to catheterization laboratory by emergency teams reduces door-to-balloon time. van de Loo A, Saurbier B, Kalbhenn J, Koberne F, Zehender M. Universitätsklinik Freiburg, Department of Cardiology, Germany. Primary percutaneous coronary intervention (PCI) is the recommended revascularization strategy for patients presenting with acute ST-elevation myocardial infarction (STEMI). In most hospitals, transfer of patients with STEMI is organized from the emergency site via emergency room (medical and cardiologic evaluation) and then to the catheterization laboratory. HYPOTHESIS: In this prospective study, we sought to evaluate the effect of a logistic modification in this treatment process. METHODS: Local emergency ambulance teams were instructed to identify and evaluate patients with STEMI eligible for direct PCI and to transport them directly to the cardiac catheterization laboratory for immediate percutaneous coronary intervention ("ER bypass"). This study prospectively included 74 consecutive patients with acute coronary syndromes (STEMI) and compared them with a matched historic control group ("ER evaluation"). Primary endpoint was the reduction in door-to-balloon time; secondary endpoint was quality of preclinical emergency diagnosis. RESULTS: Median door-to-balloon time was reduced by 27 min. Primary interventional success was achieved in 92% of patients. Preclinical emergency diagnoses were correct in 95% of patients. CONCLUSION: The preclinical emergency diagnosis of STEMI was reliable. Direct transport of patients with STEMI to the cardiac catheterization laboratory and early preclinical alert by the interventional PCI team significantly reduces door-to-balloon-times compared with established standard processes-of-care for patients considered for primary PCI 我们还有巨大差距！

12 策略上的争论

13 易化 PCI 易化 PCI 是指发病 12 h 内拟行 PCI 的患者于 PCI 前使用血栓溶解药物，以期缩短开通IRA 时间 ， 使药物治疗和 PCI 更有机结合 以 ASSENT 4 为代表的临床研究结果表明，易化PCI 结果劣于直接 PCI。目前已完全否定了应用全量溶栓剂后立即行易化 PCI 的策略 然对出血风险很低的轻、高危的 STEMI 患者 90 min不能立即 PCI 时可考虑应用 经皮冠状动脉介入治疗指南(2009)-中华医学会心血管病学分会

14

15 易化 PCI组不良反应发生率的增高主要原因：
荟萃分析： Keeley等对比较直接 PCI和易化PCI疗效的 17项随机对照临床试验进行了，所纳入STEM I患者数分别为 2 267例和 2 237例 最终冠脉血流达到 TIMI 3级者的比例相似 ( 89% vs 88% )：易化PCI组冠脉血流在术后立即达到 TIMI 3级者多于直接PCI组 (37% vs 15% ) 易化 PCI组死亡率较高(5% vs 3%)： 非致死性M I率较高 (3% vs 2% ) ，靶血管的紧急血运重建率较高 (4% vs 1% ) ，大出血率也较高 (7% vs 5% ) 易化 PCI组不良反应发生率的增高主要原因： 溶栓药易化 PC I亚组出血性脑卒中和总的脑卒中发生率均显著增高 (分别为 0 . 7% vs 0 . 1%和 1 . 1% vs 0 . 3% )。

16 产生机理 可能是早期激活血小板的副作用，无有效的抗血小板作用 动脉粥样硬化斑块出血 可能溶栓到PCI时间短 缺乏良好的抗血小板治疗

17 TRANSFER-AMI Trial

18 Background Patients with STEMI in the hospitals that do not have the capability of PCI often cannot undergo timely primary PCI and therefore receive fibrinolysis The role and optimal timing of routine PCI after fibrinolysis have not been established.

19 Methods Randomized; nonblinded trial; 52 sites in three provinces in Canada 1059 high-risk patients with STEMI and who were receiving fibrinolytic therapy at centers that did not have the capability of performing PCI All patients received aspirin, tenecteplase, and heparin or enoxaparin; concomitant clopidogrel was recommended The primary end point was the composite of death, reinfarction, recurrent ischemia, new or worsening congestive heart failure, or cardiogenic shock within 30 days

20

21 Results 88.7% of the patients assigned to standard treatment a median of 32.5 hours after randomization and in 98.5% of the patients assigned to routine early PCI a median of 2.8 hours after randomization At 30 days, the primary end point occurred in 11.0% of the patients who were assigned to routine early PCI and in 17.2% of the patients assigned to standard treatment (P=0.004) There were no significant differences between the groups in the incidence of major bleeding

22 Conclusions Among high-risk patients who had a myocardial infarction with ST-segment elevation and who were treated with fibrinolysis, transfer for PCI within 6 hours after fibrinolysis was associated with significantly fewer ischemic complications than was standard treatment.

23 院前用药的变化

24 是否需要增加氯吡格雷的负荷量

25 氯吡格雷600mg可以更迅速地 抑制血小板聚集 * * * * 600mg LD 2小时的抑制水平与300mg LD 6小时相当
103名非ST段抬高的ACS患者随机分配接受 300、600或900 mg 氯吡格雷 50 5 μmol/L ADP 900 mg * * 40 900 mg 600 mg * 300 mg 30 抑制血小板聚集 (%) 600 mg 关键信息：在非ST段抬高型急性冠脉综合症的低中危患者，给予LD >300 mg 氯吡格雷起效更快。 ALBION研究:103名无ST段抬高的急性冠脉综合症患者随机接受300mg，600mg或900mg氯吡格雷负荷剂量。 300mg LD 组在首次服用氯吡格雷后6小时，ADP诱导的PA 最大抑制程度为5mol/l 。而更高剂量的LDS组可以更早期达到最大抑制率（在前6小时，300mg组与600mg组和900mg组相比，在3个时间点均为p<0.05 ） 与标准的300mg LD相比，600mg LD在前两小时达到更好的血小板抑制效果。 研究结果提示，600mg和900mg氯吡格雷较300mg可以更加完全地拮抗P2Y12受体，从而更快抑制血小板活化和聚集。 * 20 300 mg 10 *p<0.05 与300 mg相比 1 2 3 4 5 6 时间(小时) 600mg LD 2小时的抑制水平与300mg LD 6小时相当 Montalescot et al. JACC 2006;48:931-8 Montalescot et al. JACC 2006;48:931-8

26 高负荷剂量未显著增加出血 300 mg n = 35 600 mg n = 34 900 mg 住院期间出血例数* 严重 中等 微量 总计
1 10 11 13 14 Severe bleeding (including fatal bleeding): documented intracranial haemorrhage or bleeding that causes haemodynamic compromise requiring blood or fluid replacement, inotropic support, ventricular assist devices, surgical intervention, or CPR to maintain a sufficient cardiac output Moderate bleeding: bleeding that requires transfusion of blood but does not lead to haemodynamic compromise requiring intervention Mild bleeding: bleeding not requiring transfusion and not causing haemodynamic compromise. This includes subcutaneous bleeding, mild hematomas, oozing from puncture sites, etc. *按 GUSTO 分级定义

27 ARMYDA-2: 600mg负荷剂量显著降低主要终点事件
14% 12% 12% p = 0.041 10% 死亡、心梗及靶血管血运重建% 8% 6% 4% 4% 2% 0% 600mg 300mg Patti G. et al, Circulation. 2005; 111:

28 600mg的波立维负荷剂量可降低 血栓事件的发生率
292名连续接受300或600 mg 氯吡格雷负荷剂量支架植入的NSTE ACS患者 100 12.5 600 mg 300 mg 95 10.0 600 mg p<0.0024 90 7.5 无心血管事件生存 (%) 事件率 (%) 85 关键信息:NSTE ACS患者在PCI前接受600mg氯吡格雷负荷剂量较300mg剂量可以在围手术期间更好地抑制血小板功能，减少缺血事件复发。 共292名接受冠脉支架植入术的NSTE ACS连续患者在经皮冠脉介入术前至少12小时接受300mg（n＝146）或600mg（n＝146）负荷剂量氯吡格雷。在经皮冠脉介入术前服药后取单个血样，分析ADP介导的血小板聚集的最大密度，及血小板表面P选择素的表达情况。同时记录1个月内的CV事件发生率。 两组的人口统计学、临床及治疗相关变量均一致。 所有患者均在随访的1个月内接受氯吡格雷75mg和阿司匹林160mg治疗。 所有接诊医生和负责登记临床终点事件的记录者均对血小板检查结果不知情。 接受600mg氯吡格雷治疗的患者，ADP介导的血小板聚集及P选择素表达均较300mg组显著降低（平均SD: 50 ±19%比61 ±16%, p<0.0001，0.37AU比 0.60AU，p< ）。 临床终点事件包括下列CV事件:CV死亡，急性或亚急性支架内血栓形成， ACS复发，脑卒中。随访的事件由专门的临床观察者记录。 在1个月的随访期内，300mg组中18名患者出现CV事件（12％），600mg组中7名患者出现CV 事件（5%）(P=0.02),调整传统的CV危险因素后，该差异仍不受影响（P＝0.035）。 300mg组中15名患者因ACS复发再次入院（2名为急性支架内血栓形成），2名患者脑卒中，1名出现CV死亡；而600mg组中仅6名患者因ACS复发入院（其中1名为急性支架内血栓形成），1名患者脑卒中。 两组中均无患者出现术后大出血或需要输血治疗。 5.0 300 mg 80 2.5 10 20 30 心血管事件 ACS 事件 ST* 脑卒中 心血管 死亡 时间(天) ST* = 支架血栓形成 Cuisset et al. J Am Coll Cardiol 2006; 48:1339–45 Cuisset et al. J Am Coll Cardiol 2006; 48:1339–45

29 GPⅡb/Ⅲa受体拮抗剂在STEMI的临床应用

30 2009中国经皮冠状动脉介入治疗指南 PCI术的药物治疗 Ⅰ Ⅱa Ⅱb Ⅲ
UA/NSTEMI行PCI的患者，如未服用氯吡格雷，应给予一种血小板糖蛋白IIb/IIIa受体拮抗剂。 A B 在实施诊断性CAG前或PCI术前即可给药均可。 UA/NSTEMI行PCI的患者，如已服用氯吡格雷，可同时给予一种血小板糖蛋白IIb/IIIa受体拮抗剂。 B B STEMI行PCI的患者，可尽早应用血小板糖蛋白IIb/IIIa受体拮抗剂。 接受择期PCI并置入支架的高危患者或高危病变（如ACS、近期MI、桥血管狭窄、冠状动脉慢性闭塞病变及CAG可见的血栓病变等），可应用血小板糖蛋白IIb/IIIa受体拮抗剂，但应充分权衡出血与获益风险。 B 33

31 FINESSE Trial

32

33 Results A total of 2452 patients were randomly assigned to a treatment group Significantly more patients had early ST-segment resolution with combination-facilitated PCI (43.9%) than with abciximab-facilitated PCI (33.1%) or primary PCI (P =0.01 and P =0.003, respectively). The primary endpoint occurred in 9.8%, 10.5%, and 10.7% of (P =0.55) 90-day mortality rates were 5.2%, 5.5%, and 4.5%, respectively (P = 0.49).

34 Conclusions Neither facilitation of PCI with reteplase plus abciximab nor facilitation with abciximab alone significantly improved the clinical outcomes, as compared with abciximab given at the time of PCI, in patients with ST-segment elevation myocardial infarction.

35 Prehospital Tirofiban in AMI
ON-TIME Studies Prehospital Tirofiban in AMI 在急性心梗患者给予院前应用替罗非班 ON-TIME 1: No significant benefit for low bolus dose Tirofiban in AMI 低负荷剂量、不提前使用替罗非班在急性心梗中的应用无显著获益 ON-TIME 2 Registry Study : 注册研究 Open label Tirofiban, high bolus dose 开放标签，高剂量替罗非班 ( N=416, Zwolle + Nieuwegein) ON-TIME 2 Randomized Study : 随机研究 Tirofiban high bolus dose double-blind 高负荷剂量替罗非班 What is the ON-TIME-2 study? The ON-TIME study family investigates the use of tirofiban in patients with ST elevation myocardial infarction. The ON-TIME-1 study showed no significant benefit for low dose of tirofiban in acute myocardial infarction. That is, however, the labeled dose. Other studies found that this dose may be too low. Therefore, we investigated a higher dose, about 2.5 times higher, in the ON-TIME-2 registry. And this was followed by the ON-TIME-2 randomized study which I'd like to present to you in the following. 何为ON-TIME2研究？ON-TIME这一组研究都是关于替罗非班用于ST段抬高心梗患者的研究。ON-TIME1表明低剂量替罗非班在急性心梗中的应用未带来显著获益。这个低剂量是说明书的剂量。很多其他研究发现这个剂量可能太低了。因此，我们在ON-TIME 2研究中采用一个高剂量，大约高2.5倍。且这个高剂量倍后续进行的ON-TIME2随机研究延续使用。以下就是我要介绍给你们的这个研究。 Hamm CW et al. Abstract Presented April 1, 2008, at the American College of Cardiology 57th Annual Meeting in Chicago, IL. 38

36 ON-TIME -2 转运 PCI 手术室 PCI *Bolus: 25 µg/kg & 0.15 µg/kg/min infusion
在救护车或转诊中心被确诊为急性心梗(STEMI) ASA mg Clopidogrel + UFH N=984 6/ /2007 安慰剂 替罗非班 转运 冠脉造影 PCI 手术室 冠脉造影 Here is the basic layout of the study. Patients with ST-elevation myocardial infarction were diagnosed in the ambulance or referral centers and received aspirin, 600mg loading dose of clopidogrel and unfractionated Heparin. Then they were randomized double-blind to placebo or high-dose tirofiban. After that they were transported by ambulance to the PCI center. Tirofiban was then in the placebo arm, allowed provisional also, given to the patient, also blinded. 研究基本方案：在救护车上或转诊中心被诊断为ST段抬高心肌梗死的患者，接受阿司匹林， 600mg负荷剂量的氯吡格雷和普通肝素治疗。然后被随机双盲地分为安慰剂组和高剂量替罗非班组。之后，通过救护车把患者送到PCI中心。安慰剂组在PCI时，同替罗非班组一样，被临时双盲地给予使用替罗非班 必要时使用替罗非班 持续使用替罗非班* PCI *Bolus: 25 µg/kg & 0.15 µg/kg/min infusion Hamm CW et al. Abstract Presented April 1, 2008, at the American College of Cardiology 57th Annual Meeting in Chicago, IL. 39

37 Event-free Survival 无事件生存率
Ongoing Tirofiban In Myocardial Infarction Evaluation Event-free Survival 无事件生存率 74.0% 66.7% This shows you the event-free survival rate of the secondary clinical endpoint over time, indicating that the tirofiban group had less events than the placebo group. 以上是无事件生存率的临床观察终点与时间的关系，结果表明替罗非班组的无事件生存率高于安慰剂组。 P = 0.012 Hamm CW et al. Abstract Presented April 1, 2008, at the American College of Cardiology 57th Annual Meeting in Chicago, IL.

38 1年全因死亡率 Double Blind Open Label N=984 N=414 ACC2009 -37% -36%
１年全因死亡率，双盲和开放标签研究均显示替罗非班组显著获益． RR: 0.78 (95% CI: , p=0.157) RR: 0.77 (95% CI: , p=0.276) ACC2009

39 Safety Endpoint: Bleeding 安全性终点：出血事件
Ongoing Tirofiban In Myocardial Infarction Evaluation Safety Endpoint: Bleeding 安全性终点：出血事件 4.0% Now given the fact that GPIIb/IIIa inhibitors can result in bleedings, this was a major endpoint as our safety endpoint in bleeding. And fortunately, we did not see a difference with respect to major bleeding. Particularly, non-CABG major bleedings were very similar. Minor bleedings – there was a trend to more frequent occurrence in the tirofiban. However, also this did not reach statistical significance. 现在的事实是，糖蛋白IIb / IIIA受体拮抗剂可导致出血，这是一个主要的安全性终点事件—出血事件。幸运的是，在主要出血事件发生率，替罗非班与安慰剂相比，没有统计学上的差异，特别是，非冠状动脉搭桥术主要出血非常相似。轻微出血-替罗非班较安慰剂有增多的趋势，然而，这还没有达到统计学意义 。 0.115 Hamm CW et al. Abstract Presented April 1, 2008, at the American College of Cardiology 57th Annual Meeting in Chicago, IL. 42

40 不同的解释 there was no significant difference in Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow or blush grade and no significant difference in major bleeding or minor bleeding. There was no significant difference in death, recurrent MI, or urgent target-vessel revascularization (TVR) between the tirofiban and placebo groups at 30 days

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42 JACC Vol. 54, No. 23, 2009 December 1, 2009:2205–41

43 也许当前最重要的工作是： 普及急性心肌梗死的急救知识

44 谢 谢！ 47

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49 导管室的准备，ED和CCU相关人员的交互培训