Ont Health Technol Assess Ser. 2004;4(10):1-65. Epub 2004 Aug 1.
One of the longest running debates in cardiology is about the best reperfusion therapy for patients with evolving acute myocardial infarction (MI). Percutaneous transluminal coronary angioplasty (ANGIOPLASTY) is a surgical treatment to reopen a blocked coronary artery to restore blood flow. It is a type of percutaneous (through-the-skin) coronary intervention (PCI) also known as balloon angioplasty. When performed on patients with acute myocardial infarction, it is called primary angioplasty. Primary angioplasty is an alternative to thrombolysis, clot-dissolving drug therapy, for patients with acute MI associated with ST-segment elevation (STEMI), a change recorded with an electrocardiogram (ECG) during chest pain.This review of the clinical benefits and policy implications of primary angioplasty was requested by the Ontario Health Technology Advisory Committee and prompted by the recent publication of a randomized controlled trial (RCT) in the New England Journal of Medicine (1) that compared referred primary angioplasty with on-site thrombolysis. The Medical Advisory Secretariat reviewed the literature comparing primary angioplasty with thrombolysis and other therapies (pre-hospital thrombolysis and facilitated angioplasty, the latter approach consisting of thrombolysis followed by primary angioplasty irrespective of response to thrombolysis) for acute STEMI.There have been many RCTs and meta-analyses of these RCTs comparing primary angioplasty with thrombolysis and these were the subject of this analysis. Results showed a statistically significant reduction in mortality, reinfarction, and stroke for patients receiving primary angioplasty. Although the individual trials did not show significant improvements in mortality alone, they did show it for the outcomes of nonfatal reinfarction and stroke, and for an end point combining mortality, reinfarction, and stroke. However, researchers have raised concerns about these studies.A main concern with the large RCTs is that they lack consistency in methods. Furthermore, there is some question as to their generalizability to practice in Ontario. Across the RCTs, there were differences in the type of thrombolytic drug, the use of stenting versus balloon-only angioplasty, and the use of the newer antiplatelet glycoprotein IIb/IIIa. The largest trial did not offer routine follow-up angioplasty for patients receiving thrombolysis, which is the practice in Ontario, and the meta-analysis included trials with streptokinase, an agent seldom used in hospitals in Ontario. Thus, the true magnitude of mortality benefit can only be surmised from head-to-head comparisons of current standard therapies for primary angioplasty and for thrombolysis.By taking a more restrictive sample of the available studies, the Medical Advisory Secretariat conducted a review that was more consistent with patterns of practice in Ontario and selected trials that used accelerated alteplase as the thrombolytic agent.Results from this meta-analysis suggest that the rates for primary angioplasty are significantly better for mortality, reinfarction, and stroke, in the short term (30 days), and for mortality, reinfarction, and the combined end point at 6 months. When primary angioplasty was compared with in-hospital thrombolysis, results showed a significant reduction in adverse event rates associated with primary angioplasty. However, 1 large RCT of pre-hospital thrombolysis (i.e., thrombolysis given by paramedics before arriving at the hospital) compared with primary angioplasty documented that pre-hospital thrombolysis is an equivalent intervention to primary thrombolysis in terms of survival. Furthermore, a meta-analysis of studies that compared pre-hospital thrombolysis with in-hospital thrombolysis showed a reduction in all hospital mortality rates in favour of pre-hospital thrombolysis, supporting the findings of the pre-hospital thrombolysis study. (2)Clinical trials to date have reported that hospital stay is often reduced for patients who receive primary angioplasty compared with thrombolysis. Using a cost-analysis performed alongside the only study from Ontario, the Medical Advisory Secretariat concluded that there might be savings associated with primary angioplasty. These savings may partly offset the investment the provincial government would have to make to increase access to this technology. These savings should also be shown outside of a clinical trial protocol if the overall efficiencies of primary angioplasty are to be verified.Based on this health technology policy analysis, the Medical Advisory Secretariat concludes that primary angioplasty has advantages with respect to mortality and combined end points compared with in-hospital thrombolysis (Level 1 evidence). However, pre-hospital thrombolysis improves survival compared with in-hospital thrombolysis (Level 1 evidence) and is equivalent to primary angioplasty (Level 1 evidence).Results from the literature review raise concerns about the loss of therapeutic advantage due to treatment delays, time lapse from symptom onset to revascularization, time-of-day variations, the hospital volume of procedures, and the ability of hospitals to achieve in practice what RCTs have shown.Furthermore, questions relevant to applying primary angioplasty widely, involve the diagnosis by paramedics, ambulance diversion protocols, paramedic training, and inter-hospital transfer protocols. These logistical considerations need to be addressed to realise the potential to improve patient outcomes. In its analysis, the Medical Advisory Secretariat concludes that it is unrealistic to reorganise the emergency medical services across Ontario to fully implement a primary angioplasty program.Finally, it is important to evaluate the potential of this technology in the context of Ontario's health system. This includes urban and rural considerations, the ability to expand access to primary angioplasty and to minimize symptom-to-assessment time through a diverse strategy including public awareness. Therefore, a measured, evaluative approach to adopting this technology is warranted.Furthermore, the alternative approach to pre-hospital or early thrombolysis, especially within 120 minutes from onset of symptoms, should be considered when developing the approach to improving outcomes for acute MI. This could include efforts to decrease the symptom-to-thrombolysis time through strategies such as a concerted public education program to expedite presentation to emergency rooms after onset of symptoms, a pre-hospital ECG and thrombolysis checklist in ambulances to reduce door-to-needle time on arrival at emergency rooms, and, especially in remote areas, access to pre-hospital thrombolysis.The Medical Advisory Secretariat therefore recommends that this analysis of primary angioplasty be viewed in the overall context of all interventions for the management of acute MI and, in particular, of improving access to primary angioplasty and maximising the use of early thrombolysis.Outcomes for patients with acute MI can be improved if efforts are made to optimise the interval from symptom onset to thrombolysis or angioplasty. This will require concerted efforts, including public awareness through education to reduce the symptom-to-emergency room time, and maximising efficiencies in door-to-intervention times for primary angioplasty and for early thrombolysis.Primary angioplasty and early thrombolysis cannot be considered in isolation from one another. For example, patients who have persistent STEMI 90 minutes after receiving thrombolysis should be considered for angioplasty ("rescue angioplasty"). Furthermore, for patients with acute MI who are in cardiac shock, primary angioplasty is considered the preferred intervention. The concomitant use of primary angioplasty and thrombolysis ("facilitated angioplasty") is considered experimental and has no place in routine management of acute MI at this time. In remote parts of the province, consideration should be given to introducing pre-hospital thrombolysis as the preferred intervention through upgrading a select number of paramedics to advanced care status.
心脏病学领域持续时间最长的争论之一是关于进展期急性心肌梗死（MI）患者的最佳再灌注治疗方法。经皮腔内冠状动脉成形术（血管成形术）是一种外科治疗手段，用于重新开通阻塞的冠状动脉以恢复血流。它是经皮（通过皮肤）冠状动脉介入治疗（PCI）的一种类型，也称为球囊血管成形术。对急性心肌梗死患者进行该治疗时，称为直接血管成形术。直接血管成形术是对伴有ST段抬高（STEMI）的急性心肌梗死患者进行溶栓（溶解血栓的药物治疗）的替代方法，STEMI是胸痛发作时心电图（ECG）记录的一种变化。安大略省卫生技术咨询委员会要求对直接血管成形术的临床益处和政策影响进行此次审查，促成此次审查的是最近发表在《新英格兰医学杂志》上的一项随机对照试验（RCT）（1），该试验比较了转诊的直接血管成形术和现场溶栓治疗。医学咨询秘书处回顾了比较直接血管成形术与溶栓及其他治疗方法（院前溶栓和易化血管成形术，后者是指无论溶栓反应如何，先进行溶栓然后再进行直接血管成形术）治疗急性STEMI的文献。已有许多RCT以及对这些RCT的荟萃分析比较了直接血管成形术与溶栓治疗，这些是本分析的主题。结果显示，接受直接血管成形术的患者在死亡率、再梗死率和中风发生率方面有统计学意义的降低。尽管个别试验未显示单独死亡率有显著改善，但在非致命性再梗死和中风结局以及将死亡率、再梗死率和中风综合作为一个终点时显示有改善。然而，研究人员对这些研究提出了担忧。大型RCT的一个主要问题是它们在方法上缺乏一致性。此外，对于它们在安大略省实践中的普遍适用性也存在一些疑问。在各个RCT中，溶栓药物类型、使用支架与单纯球囊血管成形术以及使用新型抗血小板糖蛋白IIb/IIIa方面存在差异。最大的试验没有为接受溶栓治疗的患者提供常规的后续血管成形术，而这是安大略省的做法，并且荟萃分析纳入了使用链激酶的试验，而链激酶在安大略省医院很少使用。因此，只能通过对直接血管成形术和溶栓治疗的当前标准疗法进行直接比较来推测死亡率获益的真实程度。通过对现有研究采用更具限制性的样本，医学咨询秘书处进行了一项与安大略省实践模式更一致的审查，并选择了使用加速阿替普酶作为溶栓剂的试验。该荟萃分析的结果表明，直接血管成形术在短期（30天）的死亡率、再梗死率和中风发生率方面以及在6个月时的死亡率、再梗死率和综合终点方面显著更优。当将直接血管成形术与院内溶栓进行比较时，结果显示与直接血管成形术相关的不良事件发生率显著降低。然而，一项将院前溶栓（即护理人员在到达医院前进行溶栓）与直接血管成形术进行比较的大型RCT记录显示，院前溶栓在生存方面是与直接血管成形术等效的干预措施。此外，一项比较院前溶栓与院内溶栓的研究的荟萃分析显示，院前溶栓有利于降低所有医院的死亡率，支持了院前溶栓研究的结果。（2）迄今为止的临床试验报告称，与溶栓治疗相比，接受直接血管成形术的患者住院时间通常会缩短。医学咨询秘书处利用与安大略省唯一一项研究同时进行的成本分析得出结论，直接血管成形术可能会节省费用。这些节省的费用可能部分抵消省政府为增加该技术的可及性而必须进行的投资。如果要验证直接血管成形术的总体效率，这些节省的费用也应在临床试验方案之外得到体现。基于这项卫生技术政策分析，医学咨询秘书处得出结论，与院内溶栓相比，直接血管成形术在死亡率和综合终点方面具有优势（1级证据）。然而，院前溶栓与院内溶栓相比可提高生存率（1级证据），并且与直接血管成形术等效（1级证据）。文献综述的结果引发了对因治疗延迟、从症状发作到血管再通的时间间隔、一天中的不同时间、医院手术量以及医院在实践中实现RCT所显示效果的能力而导致治疗优势丧失的担忧。此外，与广泛应用直接血管成形术相关的问题涉及护理人员的诊断、救护车分流方案、护理人员培训以及医院间转运方案。要实现改善患者结局的潜力，就需要解决这些后勤方面的考虑因素。医学咨询秘书处在其分析中得出结论，全面重组安大略省的紧急医疗服务以全面实施直接血管成形术项目是不现实的。最后，在安大略省卫生系统的背景下评估这项技术的潜力很重要。这包括城市和农村方面的考虑、扩大直接血管成形术可及性的能力以及通过包括提高公众意识在内的多种策略将症状出现到评估的时间减至最短。因此，采用这项技术需要采取审慎、评估性的方法。此外，在制定改善急性心肌梗死结局的方法时，应考虑院前或早期溶栓的替代方法，尤其是在症状发作后120分钟内。这可能包括通过以下策略努力缩短症状出现到溶栓的时间：开展协同的公众教育项目以加快症状发作后前往急诊室的速度、在救护车上配备院前心电图和溶栓清单以减少到达急诊室后的门到针时间，特别是在偏远地区，提供院前溶栓服务。因此，医学咨询秘书处建议，应在急性心肌梗死所有管理干预措施的整体背景下看待对直接血管成形术的此次分析，尤其是在改善直接血管成形术的可及性和最大限度地使用早期溶栓方面。如果努力优化从症状发作到溶栓或血管成形术的时间间隔，急性心肌梗死患者的结局可以得到改善。这将需要协同努力，包括通过教育提高公众意识以减少症状出现到急诊室的时间，以及最大限度地提高直接血管成形术和早期溶栓的门到干预时间效率。直接血管成形术和早期溶栓不能相互孤立地考虑。例如，溶栓治疗90分钟后仍有持续性STEMI的患者应考虑进行血管成形术（“补救性血管成形术”）。此外，对于处于心源性休克的急性心肌梗死患者，直接血管成形术被认为是首选干预措施。同时使用直接血管成形术和溶栓（“易化血管成形术”）被认为是试验性的，目前在急性心肌梗死的常规管理中没有地位。在该省偏远地区，应考虑通过将一些护理人员升级为高级护理人员来引入院前溶栓作为首选干预措施。
