急性心肌梗死的介入治疗策略

第三节　急性心肌梗死的介入治疗策略

一、急性心肌梗死的定义

过去，在WHO有关疾病发生率的研究中，具备下述三个特征中的两个即可诊断急性心肌梗死（Acute Myocardial Infarction，AMI）：典型症状（即胸痛）、心肌酶升高和出现Q波的典型心电图表现。目前人们对AMI的诊断定义有所改变，WHO三项诊断标准中的心肌酶升高，改为心肌标记物和/或心肌酶升高。由于现有技术能够识别重量＜1g的心肌坏死，使得M I诊断标准敏感性增高。ST段抬高的AM I（STEMI）往往伴有明确心肌标志物和心肌酶升高，诊断与以前相同；非ST段抬高AM I（NSTEM ）I需与UA区分，以往根据心肌酶是否升高，现根据心肌标志物肌钙蛋白水平给予诊断：即肌钙蛋白＜0.1μg/mL，诊断为UA；肌钙蛋白＞0.1μg/mL但＜1μg/mL，诊断为高危UA；肌钙蛋白＞1μg/ml，诊断为NSTEM I。

二、急性心肌梗死的分类

在溶栓治疗时代之前，临床医师根据AM I后数天内的心电图（ECG）检查，通常将AM I病人分为Q波AM I与无Q波AM I。Q波AM I通常认为是透壁梗死，无Q波AM I则常指内膜下梗死。在对AM I病理生理了解取得进展的基础上，重新认识了AM I的表现形式，提出了急性冠状动脉综合征这一概念，根据是否适合再灌注疗法将其疾病谱分为UA、NSTEM I和STEM I。并非所有的STEM I都会演变成Q波心肌梗死，NSTEM I也可以发生Q波。实际上，AM I中大多数ST段抬高的患者最终发生急性Q波M I，少数发生急性非Q波M I。多数非ST段抬高的患者的12导联ECG上没有Q波，既非Q波M I，仅少数非ST段抬高的患者的ECG上有Q波，诊断为Q波M I。ECG缺乏足够的敏感性和特异性，不能可靠地鉴别透壁性心肌梗死和内膜下心肌梗死。因为透壁性M I可以不产生Q波，而Q波也可能出现在尸体解剖证实是内膜下（非透壁性）AMI病人的ECG上。

三、AM I的介入治疗

AM I再灌注治疗目标是尽早、完全和持久地重建因IRA闭塞所致的功能与存活受到严重威胁的心肌组织血流。AMI再灌注治疗的理想目标是梗死心肌组织水平血流的持续完全恢复。如前所述，尽管多项大规模研究表明溶栓治疗可降低死亡率，改善左心室功能，但溶栓治疗仍存在许多不足之处：①静脉溶栓的再通率仅为60%～80%，且再通后仍有残余狭窄；②仅50%～56%患者溶栓后冠脉血流可达TIM I3级，而TIM I 2级血流虽然达再通标准，但死亡率下降不明显，再梗死率高；③溶栓后心肌缺血复发或冠状动脉再闭塞率为15%～30%；④有1%～2%的出血并发症；⑤50%左右的病人因溶栓禁忌证而不能接受溶栓治疗。1983年，Hartzler等首先报道，AM I患者未经溶栓治疗，而直接行经皮经腔冠状动脉球囊成形术（PTCA）获良好效果。在后来大约10年间，共有10项随机对照研究就直接经皮冠状动脉成形术与静脉溶栓治疗的效果进行比较，同时尚有多项研究对比溶栓治疗后早期和晚期进行介入治疗的效果，逐渐肯定了急诊经皮冠脉介入治疗（PC）I作为AM I治疗的新的更为有效的治疗策略，并伴随着心血管医学的进步不断走向成熟，使其近年来在有条件的单位成功替代溶栓治疗，成为STEM I和NSTEM I高危病人的首选治疗方案。

根据AM I发生后行PCI的时间及与溶栓的关系分为：①直接PCI；②溶栓后PCI，包括即刻PCI与补救性PCI；④急性期后的PCI，主要指延期PCI与出院前冠状动脉造影PCI。

1.直接PCI对AMI患者未采取溶栓治疗而直接进行PCI。目的是恢复血流灌注、挽救濒死心肌。与溶栓治疗相比，IRA再通率高，达到TIM I3级血流者95%，再闭塞率低，缺血复发少，且出血（尤其脑出血）的危险性低。最近发表的SHOCK试验的资料表明，对AM I并发心源性休克患者，直接PCI与药物治疗（包括主动脉内球囊反搏，IABP）和溶栓治疗比较，可明显降低6个月病死率。但是直接PCI也有一定的局限性，如需要技术熟练的介入心脏病医师，对设备等硬件要求高。

（1）公认适应证（Ⅰ类）：①伴有ST段抬高或新出现的完全性左束支传导阻滞（LBBB）的AM I患者，可以在发病12h内行直接PCI；或是发病12h后仍有症状者，可行直接PCI。②伴有ST段抬高或新出现的完全性LBBB的M I患者，发病36h内发生心源性休克，年龄＜75岁，可以在休克发生18h内行直接PCI。

（2）一般适应证（Ⅱa类）：适合再灌注治疗，但有溶栓治疗禁忌证的AM I患者。

（3）相对禁忌证：M I急性期治疗非IRA；已经溶栓治疗，临床判断IRA开通，没有心肌缺血的症状；发病已经超过12h，目前没有心肌缺血的证据；术者经验不足。

2.溶栓后PCI

（1）即刻PCI（Immediate PCI）：是对溶栓治疗成功、IRA造影示TIM I3级血流、没有明显缺血症状的患者治疗狭窄病变。早期资料显示，即刻PCI对挽救缺血心肌、预防再梗死和降低死亡率没有明显益处。甚至有试验显示，溶栓治疗成功后即刻球囊扩张可使穿刺部位血管出血、心肌缺血复发，使急诊冠状动脉旁路手术和死亡等并发症增加。但应该强调，支架应用已经使以上并发症明显减少。近期有资料显示，对于残余狭窄＞75%的IRA病人，由于其短期内容易出现再缺血发作，介入治疗仍然优于保守治疗。

（2）补救性PCI：溶栓治疗失败后，患者仍然有持续胸痛或反复心肌缺血，IRA未达到TIM I3级血流，此时行PCI使闭塞的血管再通。随机临床试验证实，补救性PCI与延迟PCI相比，能使IRA通畅率增加，改善梗死周围区域的室壁运动，降低住院病死率和心力衰竭发生率。但在非前壁STEM I的患者未取得类似结果。应该注意溶栓药物对PCI的影响，溶栓药物只能溶解血栓的纤维蛋白成分，暴露出来的凝血酶不仅可以激活更多的凝血酶原，而且是最强的天然血小板聚集的激活剂，此时补救性PCI的血栓并发症可能高于直接PCI。另外，溶栓药物、UFH、抗血小板药物的联合应用也可能增加局部或内脏出血的可能性。补救性PCI也有限度，冠状动脉阻塞超过3h，已发生大面积的心肌坏死，症状出现至患者到大医院输入溶栓剂、溶栓失败的识别和随后启动PCI这些带来的时间延迟，导致补救性PCI不能挽救大部分心肌。虽然溶栓后90min IRA的开通率只有50%～85%，但到24h可达90%。这种晚期的再灌注可以提高生存率，没有溶栓联合介入带来的危险。

（3）适应证：①溶栓后仍有明显胸痛，ST段抬高无显著回落，临床提示未再通或有再梗死证据者，为补救性PCI公认的适应证（Ⅰ类）；②溶栓后心源性休克或血流动力学不稳定者可行PCI（Ⅱa类）。

（4）禁忌证：溶栓失败后48～72h常规PCI；溶栓成功后即刻PCI治疗残余狭窄≤75%的IRA，造影示TIMl3级血流，均属于相对禁忌证。

3.急性期后的PCI出院前常规行冠状动脉造影和PCI的意义尚有争论。DANAM I试验显示，如果患者运动试验有缺血，积极的血管重建治疗优于药物保守治疗。再灌注治疗AM I的主要机制被认为是挽救濒临坏死的缺血心肌。但许多证据表明，即使在数小时或数天后开通IRA也能改善预后，其机制不是挽救心肌，而是预防梗死区扩张和膨胀、左心室重构和恶性室性心律失常，这些都有利于改善AM I患者的生存率。鉴于冠状动脉造影能提供重要的解剖、功能和预后的信息，而且比较安全，AM I患者可在出院前行冠状动脉造影，并根据情况做血管重建治疗。

（1）有自发或诱发的心肌缺血，持续血流动力学不稳定者，为公认的适应证（Ⅰ类）。

（2）左心室射血分数＜40%、左心衰竭、严重室性心律失常者，大多认为应行PCI（Ⅱa类）。

（3）PCI开通闭塞的IRA；对所有非Q波M I患者行PCI；急性期出现过左心衰竭，但左心室射血分数＞40%者，也可考虑行PCI，但其价值尚待证实（Ⅱb类）。

（4）AMI 48h内无自发或诱发的心肌缺血者；PCI开通闭塞的IRA属于相对禁忌证。

4. AM I PCI时冠状动脉支架植入术的应用虽然AM I直接PTCA疗效较好，但仍有些不足之处有待改进。直接PTCA成功后仍有10%～17%患者有反复心肌缺血发生；5%～10%患者IRA术后出现急性和/或亚急性闭塞；30%～50%患者于6个月内出现再狭窄，需要进行血运重建术。早期认为IRA病变处富含血栓，不宜常规植入支架，只限于应急情况时使用。

根据Zwolle、Stent-PAM I和CADILLAC等研究资料，比较直接支架植入与直接PTCA的随机对照研究结果，说明常规植入支架在降低心脏事件发生率和减少靶血管重建方面优于直接PTCA。因此，支架植入术应该常规用于AM I患者的PCI。

5. GPⅡb/Ⅲa受体拮抗剂在急性心肌梗死PCI中的应用如前所述，糖蛋白Ⅱb/Ⅲa受体的激活是血小板聚集的最后共同通道，高危患者PCI中应用糖蛋白Ⅱb／Ⅲa受体拮抗剂可降低主要心血管事件（MACE）发生率已被充分证实。TIM I-14试验、SPEED试验和GRAPE试验结果显示，AMⅠ患者应用阿昔单抗后90min内有18%～32%患者达到TIM I3级血流再灌注（平均为23%），较GUSTOⅡb试验的8%自发性再通率为高。基于上述理由，AM I早期应用GPⅡb/Ⅲa受体拮抗剂有可能使部分病人尽早达到再通，克服PCI手术需运送或等候所造成的时间延迟；PCI前达到再灌注可以最大限度地保护心功能，提高疗效；此外，应用GPⅡb/Ⅲa受体拮抗剂可降低术后缺血事件。SPEED试验结果提示术前用药能提高PCI疗效。CADILLAC试验结果提示AMI支架植入术效果优于单纯PTCA；支架植入术合并使用阿昔单抗效果优于不合并使用该药，可使6个月无事件率增加。ISAR-2试验显示，GPⅡb/Ⅲa受体拮抗剂可使AM I支架术后14天血流峰值速度加快，血流储备增加。ADM IRAL试验结果显示，AM I支架术合并使用GP IIb/IIIa受体拮抗剂可增加成功率，增加TIM I3级率，改善心功能，改善预后。

目前的资料充分显示AM I支架术合并使用GPⅡb/Ⅲa受体拮抗剂的益处：早期使用可使更多的患者于PCI前达到再灌注；可增加6个月无事件率；减少TVR和增加无事件生存率。

ACC/AHA建议：

Ⅱa类：STEM I患者在直接PCI术前（行或不行支架术）最好尽早应用阿昔单抗（证据级别B）。

Ⅱb类：STEM I患者在直接PCI术前（行或不行支架术）可给予替罗非班或依替巴肽治疗（证据级别C）。

6.改善心肌微循环、心肌保护有学者提出TIM I血流分级仅反映心外膜冠状动脉血流，而部分患者虽然达到TIM I3级血流，但心肌微血管循环差，这部分病人心功能受损较明显，预后较差。因此，AM I再灌注治疗不但要尽量达到TIM I3级血流，而且要达到较好的心肌微血管循环。

改善心肌微血管循环目前处于研究阶段，主要的研究方向为：①药物治疗，通过Ⅱb/Ⅲa受体拮抗剂减少血栓栓塞的机会；通过腺苷、cariporide改善心肌代谢；②远端保护装置，如Angioguard、PercuSurge等，将血栓过滤并吸出体外，防止远端血管栓塞；③过滤器，可过滤白细胞、CD18等；④物理方法，如降低体温；⑤血栓溶解装置，如超声溶栓Acolysis、负压吸引装置Possis AngioJet、旋切血栓吸引装置Endi- cor X-Sizer等。本中心应用Angioguard远端保护装置对25例STEM I病人进行急诊PCI，结果表明该装置与常规PCI对比，可以改善心肌血流灌注，减少梗死面积，改善心功能。

7.无心外科急诊搭桥手术能力的医院和小医院转诊病人开展急诊PCI近年的实践表明，无心外科急诊搭桥手术能力的医院一样可以开展急诊PCI手术，其结果与有心外科急诊搭桥手术能力的医院无差异。医院应达到以下要求：操作者是能正规完成择期经皮介入的有经验的医生；导管室的护士和技术人员必须熟练掌握急救和介入设备的使用，并能做到全天候服务（每年365天，每天24小时）；导管室配备齐全，包括良好的影像设备、复苏设备、临时心脏起搏器、IABP等；心脏监护室护士必须熟练掌握血流动力学监测和IABP使用；与上级医院必须有书面的协议以便能使病人立即有效地转送到最近医院的心脏内科；建立急诊介入的绿色通道，把急诊介入作为AM I患者的常规治疗选择；急诊PTCA病例选择必须严格；建立急诊PTCA的预后分析和定期阶段总结制度。近来研究表明，从小医院转送病人去中心医院做直接PCI，结果也很好，这一结果为今后急诊PCI的发展提供了一个新思路。

（王乐丰　刘晓玲　杨新春　张达鹏　李惟铭）

参考文献

[1] Davies MJ, Richardson PD, Woolf N, et al. Risk of thrombosis in human atherosclerotic plaques: Role of extracellular lipid, macrophage, and smooth muscle cell content[J]. Br Heart J, 1993, 69: 377.

[2] Falk E, Shah PK, Fuster V. Pathogenesis of plaque disruption. In Fuster V, Ross R, Topol EJ.（eds）.: Atherosclerosis and Coronary Artery Disease[M]. Philadelphia, Lippincott-Raven, 1996.

[3]Roberts WC. Preventing and arresting coronary atherosclerosis[J]. Am Heart J, 1995, 130: 580.

[4]Wilson RF, Holida MD,White CW. Quantitative angiographic morphology of coronary stenoses leading to myocardial infarction or unstable angina[J]. Circulation, 1986, 73: 286.

[5] Kovanen PT, Kaartinen J, Paavonen, T. Infiltrates of activated, mast cells at the site of coronary atheromatous erosion or rupture in myocardial infarction[J]. Circulation, 1995, 92: 1084.

[6] Braunwald E. Morning resistance to thrombolytic therapy[J]. Circulation, 1995, 91: 1604.

[7] Pfeifer MA.Braunwald E.Ventricular remodeling aftermyocardial infarction:Experimental observations and clinical implications[J].Circulation, 1990, 81:1161.

[8] Freifeld AG, Schuster EH, Bulkley BH. Nontransmural versus transmural myocardial infarction[J]. Am J Med, 1983, 75: 423.

[9] Ambrose JA, Tannenbaum MA, Alexopoulos D, et al. Angiographic progression of coronary artery disease and the development of myocardial infarction[J]. J Am Coll Cardiol, 1988, 12: 56.

[10]DeWood MA, Spores J, Notske RN, et al. Prevalence of total coronary artery occlusion during the early hours of transmural myocardial infarction[J]. N Engl J Med, 1980, 303: 897.

[11] Kinch JW, Ryan TJ. Right ventricular infarction[J]. N Engl J Med, 1994, 330: 1211.

[12]Nielsen FE,Andersen HH,Gram-Hanson P, et al. The relationship between ECG signs of atrial infarction and the development of supraventricular arrhythmias in patients with acute myocardial infarction[J]. Am Heart J, 1992, 123: 69.

[13] Alpert JS. Myocardial infarction with angiographically normal coronary arteries[J]. Arch Intern Med, 1994, 154: 265.

[14] Pfeifer MA. Left ventricular remodeling after acute myocardial infarction[J]. Annu Rev Med, 1995, 46: 455.

[15] Fitzgerald DJ, Roy L, Catella F, et al. Platelet activation in unstable coronary disease[J]. N Engl J Med, 1986, 315: 983.

[16] Lenfant C. The calcium channel blocker scare: Lessons for the future[J]. Circulation, 1995, 91: 2855.

[17] Sgarbossa EB, Pinski SL, Barbagelata A, et al. Electrocardiographic diagnosis of evolving acute myocardial infarction in the presence of left bundle-branch block[J]. N Engl J Med, 1996, 334：481.

[18] Levine HD. Subendocardial infarction in retrospect: Pathologic, cardiographic, and ancillary features[J]. Circulation, 1985, 72: 790.

[19]Meyer BJ, Chesebro JH.Aspirin and anticoagulants. In Julian D, and Braunwald E.（eds）.:Management of Acute Myocardial Infarction[M]. London,W. B. Saunders Ltd., 1994.

[20] Hjalmarson A, Elm feldt D, Herlitz J, et al. Effect on mortality of metoprolol in acute myocardial infarction, a doubleblind randomized trial[J]. Lancet, 1981, 2: 823.

[21] Kirshenbaum JM, Kloner RF, McGowan N, et al. Use of an ultrashort acting beta receptor blocker（esmolo）tin patients with acute myocardial ischemia and relative contraindications to beta-blockade therapy[J]. J Am Coll Cardiol, 1988, 12: 773.

[22] Yusuf S, Held P, Furberg C. Update of effects of calcium antagonists in myocardial infarction or angina in light of the second Danish Verapamil Infarction Trial（DAV IT-I）Iand other recent studies[J]. Am J Cardiol, 1991, 67：1295.

[23]Califf GM, Bengtson IR. Cardiogenic shock[J]. N Engl J Med, 1994, 330: 1724.

[24] Kloner RA, Shook T, Przyklenk K, et al. Previous angina alters in-hospital outcome in TIM I 4: A clinical correlate to preconditioning[J]. Circulation, 1995, 91: 37.

[25] Kloner RA, Muller J, Davis V. Effects of previous angina pectoris in patients with first acute myocardial infarction not receiving thrombolytics:M ILLS Study Group:Multicenter Investigation of the Limitation of Infarct Size[J]. Am J Cardiol, 1995, 75: 615.

[26]Granger CB, Califf RM, Topoi EJ:Thrombolytic therapy for acute myocardial infarction:A review[J]. Drugs, 1992, 44：293.

[27] Topol E. Thrombolytic intervention. In Topol, E.（ed）.: Textbook of Interventional Cardiology[M]. 2nd ed. Philadelphia, W. B. Saunders Company, 1994.

[28] TIM I Study Group: The Thrombolysis in Myocardial Infarction（TIM ）ITrial: Phase I findings[J]. N Engl J Med, 1985, 312: 932.

[29] Chesebro JH, Knatterud G, Roberts R. et al. Thrombolysis in Myocardial Infarction（TIM ）ITrial, Phase 1:A comparison between intravenous tissue plasminogen activator and intravenous streptokinase[J]. Circulation, 1987, 76: 142.

[30] ISIS-2（Second International Study of Infarct Surviva）lCollaborative Group:Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17, 187 cases of suspected acute myocardial infarction: ISIS-2[J]. Lancet, 1988, 2:349.

[31]Wilcox RG, von der Lippe G, Olsson CG, et al. Trial of tissue plasminogen activator for mortality reduction in acute myocardial infarction:Anglo-Scandinavian Study of Early Thrombolysis（ASSET）[J]. Lancet, 1988, 1: 525.

[32] Lee KL, Woodlief LH, Topol E, et al. Predictors of 30-day mortality in the era of reperfusion for acute myocardial infarction:Results from an international trial of 41,021 patients[J]. Circulation, 1995, 91: 1659.

[33] Gore JM, Granger CB, Simoons ML, et al. Stroke after thrombolysis:Mortality and functional outcomes in the GUSTO-I Trial[J]. Circulation, 1995, 92: 2811.

[34]Maggioni AP, Franzosi MG, Santoro E, et al. The risk of stroke in patients with acute myocardial infarction after thrombolytic and antithrombotic treatment[J]. N Engl J Med, 1992, 327: 1.

[35] Alexander JH. Sparapani PA, Mahaffey KW, et al. For the PURSUIT Investigators.Association between minor elevations of creatine-kinase-MB and mortality in patients with acute coronary syndromes without ST-segment elevation[J]. JAMA, 2000, 283: 347-353.

[36] Apple FS. Tissue specificity of cardiac troponin I, cardiac troponin T, and creatine kinase MB[J]. Clin Chim Acta, 1999, 284: 151-158.

[37]Harrington RA, Lincoff AM, Calif RM, et al. For the CAVEAT Investigators. Characteristics and consequences of myocardial infarction following percutaneous coronary intervention:insights from the Coronary Angioplasty Versus Excisional Atherectomomy Tria（lCAVEAT）[J]. J Am Coll Cardiol, 1995, 25: 1693-1699.

[38] Lindahl B, Venge P, Wallentin L. For the FRISC Study Group. Relation between troponin T and the risk of subsequent cardiac events in unstable coronary artery disease[J]. Circulation, 1996, 93: 1651-1657.

[39] Obman EM, Armstrong PW, Cbristenson RH, et al. For the GUSTO-IIa Investigators. Cardiac troponin I levels for risk stratification in acute myocardial ischemia[J]. N Engl J Med, 1996, 335: 1333-1341.

[40] Ottani F, Galvani M, Ferrini D, et al. Direct comparison of early elevations of cardiac troponin T and I in patients with clinical unstable angina[J]. Am Heart J, 1999, 137: 284-291.

[41] Tardiff BE. Califf RM, Tcheng JE, et al. For the IMPACT-II Investigators. Clinical outcomes after detection of elevated enzymes in patients undergoing percutaneous intervention: IMPACT-II trial（lntegrilin[eptifibatide] to Minimize Platelet Aggregation and Coronary Thrombosis-II）[J].. J Am Coll Cardiol, 1999, 33: 88-96.

[42] Zimmerrnan, Fromm R, Meyer D, et al. Diagnostic marker cooperative study for the diagnosis of myocardial infarction[J]. Circulation, 1999, 99: 1671-1677.

[43] Anderson WD,Wagner NB, Lee KL, et al. Evaluation of a QRS scoring system for estimating myocardial infarct size. VI: Identification of screening criteria for non-acute myocardial infarcts[J]. Am J Cardiol, 1988, 61: 729-813.

[44] Crow RS, Prineas RJ, Jacobs DR, et al. A new epidemiologic classification system for interim myocardial infarction from serial electrocardiographic changes[J]. Am J Cardiol, 1989, 64: 454-461.

[45] Belier GA. Assessment of myocardial viability[J]. Curr Opin Cardiol, 1997, 12: 459-467.

[46]Gibler WB. Runyon JP, Levy RC, et al. A rapid diagnostic and treatment center for patients with chest pain in the emergency department[J]. Ann Emerg Med, 1995, 25: 1-8.

[47]Machecourt J, Longere P, Fagret D, et al. Prognostic value of thallium-201 single photon emission computed tomographic myocardial perfusion imaging according to extent of myocardial defect[J]. J Am Coll Cardiol, 1994, 23: 1096-1106.

[48] Saeian K, Rhyne TL, Sagar KB. Ultrasonic tissue characterization for diagnosis of acute myocardial infarction in the coronary care unit[J]. Am J Cardiol, 1994, 74: 1211-1215.

[49] Gillum RF, Fortmann SP, Prineas RJ, et al. International diagnostic criteria for acute myocardial infarction and acute stroke[J]. Am Heart J, 1984, 108: 150-158.

[50]McGovern PG, Pankow JS, Shahar E. For the Minnesota Heart Survey Investigators.Recent trends in acute coronary heart disease-mortality, morbidity, medical care and risk factors[J]. N Engl J Med, 1966, 334: 884-890.

[51] Report of the Joint International Society and Federation of Cardiology/World Health Organization Task Force on Standard-

ization of Clinical Nomenclature. Nomenclature and criteria for diagnosis of ischemic heart disease[J]. Circulation, 1979, 59: 607-609.

[52] Porela P, Helenius H, Pulkki K, et al. Epidemiological classification of acute myocardial infarction: time for a change?[J].Eur Heart J, 1999, 20: 1459-1464.

[53] The PURSUIT Trial Investigators. Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes, The PURSUIT Trial Investigators: Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy[J]. N Engl Jmed, 1998, 339: 436-443.

[54]Newby LK, Califf RM, Guerci A, et al. Early discharge in the thrombolytic era: an analysis of criteria for uncomplicated infarctio from the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries（GUSTO）trial[J]. J Am Coll Cardiol, 1996, 27: 625-632.

[55] Maynant C, Weaver WD, Lambrew C, et al. Factors influencing the time to administration of thrombolytic therapy with recombinant tissue plasminogen activator（data from the National Registry of Myocardial Infarction）. Participants in the National Registry of Myocardial Infarction[J]. Am J Cardiol, 1995, 76: 548-552.

[56] Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms（PRISM- PLUS）Study Investigators. Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban unstable angina and non- Q- wave myocardial infarction[J]. N Engl J Med, 1998, 338: 1488-1497.

[57] Hochman Js, Tamis JE, Thonpson ID, et al. Sex, clinical presentations and outcome in patients with acute coronary syndromes. Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes IIb Investigators[J]. N Engl J Med, 1999, 341, 226-232.

[58] Jayes RLJ, Beshansky JR, D Agostlno RB, et al. Do patients′coronary risk factor reports predict acute cardiac ischemia in the emergency department? A multicenter study[J]. J Clin Epidemiol, 1992, 45: 621-626.

[59]Mueller HS, Cohen IS, Braunwald E, et al. Predictors of early morbidity and mortaliry after thrombolytic therapy of acute myocardial infarction. Analyses of patient subgroups in the Thromboysis In Myocardial Infarction（TIM ）Itrial phase II[J]. Circulation, 1992, 85: 1254-1264.

[60]White LD, Ice 1I-I, Cook EF, et al. Comparison of the natural history of new onset and exacerbated chronic ischemic heart disease. The Chest Pain Study Group[J]. J Am Coll Cardiol, 1990, 16: 304-310.

[61] Zaacks SM, Liebson PR, Calvin JE, et al. Unstabl angina and non- Q wave myocardial infarction: Does the clinical diagnosis have therapeutic implications[J]. J Am Coll Cardiol, 1999, 33; 107-118.

[62] Savonitto S, Arlissino D, Granger CB, et al. Prognostic value of the admission electrocardiogram in acute coronary syndromes[J]. JAMA, 1999, 281: 707-713.

[63] Morrow DA, Rifai N, Antman EM, et al. C-reactive protein is a potent predictor of mortality independently of and in combination with troponin T in acute coronary syndromes: a TIM I IIA substudy. Thrombolysis In Myocardial Infarction[J]. J Am Coll Cardiol, 1998, 31: 1460-1465.

[64] Yusuf S, Collins R, MacMahon S, et al. Effect of intravenous nitrates on mortality in acute myocardial infarction: an overview of the randomized[J]. Lancet, 1988, 1: 1088-1092.

[65] ACE Inhibitor Myocardial Infarction Collaborative Group. Indications for ACE inhibitors in the early treatment of acute myocardial infarction: systematic overview of individual data from 100 000 patients in randomized trials[J]. Circulation, 1998, 97: 2202-2212.

[66] Flather M, Yusuf S, Kober L, et al. Long- term ACE- inhibitor therapy in patients with heart failure or left ventricular dysfunction: a systematic overview of data from individual patients[J]. Lancet, 2000, 355: 1575-1581.

[67] Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin convening-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients.The Heart Outcomes Prevention Evaluation Study Investigators[J]. N Engl J Med, 2000, 342: 145-153.

[68] Cohen M, Demers CS, Curfinkel EP, et al. A comparison of low-molecular-weight heparin with unfractionaled heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous enoxaparin in Non-Q-Wave Coronary Events Study Group[J]. N Engl J Med, 1997, 337: 447-452.

[69] Antnkan EM, Cohen M, Radley D, et al. Assessment of the treament effect of enoxapaparin for unstable angina/non- Q-

wave myocardial infarction: TIM I lIB-ESSENCE metaanalysis[J]. Circulation, 1999, 100: 1602-1608.

[70] Cohen M, Tneronx P,Weber S, et al. Combination therapy with tirofiban and enoxaparin in acute coronary syndrpmes[J]. Int J Cardiol, 1999, 71: 273-281.

[71] Bennett CL, Connors JM, Candle JM, et al. Thrombotic thrombocytopenic purpura associated with clopidogrel[J]. N Engl J Mod, 2000, 342: 1773-1777.

[72] Klein W, Buchwald A, Hillis SE, et al. Comparison of low-molecular-weight heparin with unfractionated heparin acutely and with placebo for 6 week in the management of unstable coronary artery disease. FRagmin In unstable Coronary artery disease study（FRISC）[J]. Circulation, 1997, 96: 61-68.

[73] Topol EJ, Califf RM,Weisman HF, et al. Randomised trial of coronary intervention with antibody against plateletⅡb/Ⅲa integrin for reduction of clinical restenosis: results at six months. The EPIC Investigators[J]. lancet, 1994, 343: 881-886.

[74] Lincoff AM, Califf RM, Molitemo DJ, et al. Complmentary clinical benefits of coronaryartery stenting and blockade of platelet glycoprotein IIb/IIIa receptors: Evaluation of Platelet Ilb/IIIa Inhibition in Stenting Investigators[J]. N Engl J Med, 1999, 341: 319-327.

[75] Yusuf S, Zhao F, Mchta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation[J]. N Engl J Med, 2001, 345: 494-502.

[76]Mehta SR, Yusuf S, Petera RJ, et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention:the PCI-CURE study[J]. lancet, 2001, 358: 527-533.

[77] Zijlstra et al. PTCA vs thrombolysis in acute ST elevation M I ZWOLLE study,long term follow-up[J]. N Engl J Med, 1999, 341: 1419-1431.

[78]Weaver WD,Simes RJ,Betriu A, et al. comparison of primary coronary angioplasty and intravenous thrombolytic therapy for acute myocardial infarction,a quantitative review[J]. JAMA, 1997, 278: 2093-2098.

[79]White HD, Van de Werf FJ.Thrombolysis for acute myocardial infarction[J]. Circulation, 1998, 97: 1632-1646.

[80] Hochmann, et al. Emergency revascularization vs initial medical stablization for AM I with SHOCK trial[J]. JAMA, 2001, 285:190-192.

[81] Sanborn TA, Sleeper LA, Bates ER, et al., for the shock investigators. Impact of thrombolysis, intra-aortic balloon pump counterpulsation, and their combination in cardigenic shock complicating acute myocardial infarction: a report from the SHOCK trial registry[J]. JACC, 2000, 36: 1123-1129.

[82] 220 Grech ED, Sutton AG, Campbell PG, et al. Reappraising the role of immediate intervention following thrombolytic recanalization in acute myocardial infarction[J]. Am J Cardiol, 2000, 86（4）：400-405.

[83] Topol E, Califf R, Geoge B, et al. A randomized trial of immediate versus delayed elective angioplasty after intravenous tissue plasminogen activator in acute myocardial infarction[J]. N Engl J Med, 1987, 317: 581-588.

[84] Ross AM,Reiner JS,Greenhouse SW,et al.A randomized trial comparing Primary Angioplasty with a strategy of short-acting thrombolysis and immediate planned rescue angioplasty in acute myocardial infarction:the PACT trial[J]. JACC, 1999, 34: 1954-1962.

[85] Loubeyre C, Lefevre T, Louvard Y, et al. Outcome after combined reperfusion therapy for acute myocardial infarction, combining pre-hospital thrombolysis with immediate percutaneous coronary intervention and stent[J]. Eur Heart J, 2001, 22: 1128-1135

[86] Grines CL,Browne KF,Marco J, et al.A comparison of immediate angioplasty with thrombolytic therapy for acute myocardial infarction[J]. N Engl J Med, 1993, 328: 673-679.

[87]Madsen JK, Grande P, Saunamaki K, et al. Danish multicenter randomized study of invasive versus conservative treatment in patients with inducible ischemia after thrombolysis in acute myocardial infarction（DANAM I）. DANish trial in Acute Myocardial Infarction[J]. Circulation, 1997, 96（3）：748-755.

[88] Stone G,Grines CL,Browne KF, et al. Predictors of in-hospital and 6-month outcome after acute myocardial infarction in the perfusion era:the Primary Angioplasty in Myocardial Infarction（PAM ）Itrial[J]. JACC, 1995, 25: 370-377.

[89]Grines CL,et al.A comparison of coronary balloon angioplasty with stenting for acute myocardial infarction.Stent-PAM I trial[J]. N Engl J Med, 1999, 341: 1949-1956.

[90] Suryapranata H, van, Hoorntje JCA, et al.Randomised comparison of coronary stenting with balloon angioplasty in selected

patients with acute myocardial infarction[J]. Circulation, 1998, 97: 2502-2505.

[91] Antman EM, Giugliano RP, Gibson CM, et al.阿昔单抗facilitates the rate and extent of thrombolysis.Results of the Thrombolysis in Myocardial Infarction（TIM ）I14trial[J]. Circulation, 1999, 99: 2720-2732.

[92]Herrmann HC, Moliterno DJ, Bode C, et al. Combination of阿昔单抗and reduced-dose reteplase facilitates early PCI in acute M I: results from the SPEED trial[J]. Circulation, 1999, 100 Suppl 1: 1-188.

[93] Gruberg L, Dangas G, Leon MB, et al.Platelet glycoproteinⅡb/Ⅲa receptor antagonists during primary angioplasty and stenting for acute myocardial infarction[J]. Cardiology International autumn, 2000, 30-36.

[94] Yamada DM, Topol EJ.Microvascular embolization in acute coronary syndromes[J]. Acute coronary syndromes, 2001, 4: 9-17.

[95] Aversano T, Aversano LT, Passamani E, et al. for the Atlantic Cardiovascular Patient Outcomes Research Team（C-PORT）Thrombolytic therapy vs. primary precutaneous coronary intervention for myocardial infarction in patients presenting to hospitals without on-site cardiac surgery.A randomized controlled trial[J]. JAMA, 2002, 287: 1943-1951.

[96] Elad Y,French WJ, Shavelle DM,etal.,for the Participants in the National Registry of Myocardial Infarction Primary angioplasty and selectionbias in patients presenting late（＞12h）after onset of chest pain and ST elevation myocardial infarction[J]. JACC, 2002, 39: 826-833.

[97]Moreno R,Lopez-Seldon J,Garcia E,et al.Primary angioplasty reduces the risk of leftventricular free wall rupture compared with thrombolysis in patients with acute myocardial infarction[J]. JACC, 2002, 39: 598-603.

[98] Groch L,Widimsky P, Aschermann M, et al.Thrombolysis vs. PTCA vs. both in patients with acute myocardial infarction（Prague tria）l:narography findings and PTCA results[J]. Eur Heart J, 1999, 20 Suppl: 32.

[99]Moon JC, Kalra PR, Coats AJ. DANAM I-2: is primary angioplasty superior to thrombolysis in acute M I when the patient has to be transferred to an invasive centre?[J]. Int J Cardiol, 2002, 85（2-3）：199-201.