The Ischemia Trial - CCC

描述(由申请人提供)： 这项拟议试验的长期目标是确定侵入性方法在稳定性缺血性心脏病(SIHD)和实质性缺血患者中的作用，这项试验名为《医疗和侵入性方法健康有效性比较研究》。试验假说是，在负荷成像上，心导管置入术+完全血运重建加最佳药物治疗(OMT)优于单纯OMT作为中重度缺血患者的治疗策略。主要终点将是心血管死亡、心肌梗死(MI)或因不稳定心绞痛、复苏心脏骤停或心力衰竭而住院的时间。侵入性策略将改善生活质量的假设也将得到检验。将对成本效益进行评估。 CORAGE和BARI 2D试验发现，在根据冠状动脉解剖选择的SIHD患者中，与单纯OMT相比，冠状动脉血管重建术的初始管理策略并不能降低死亡或心肌梗死的风险。这些数据提出了在病情稳定的患者中是否需要心导管插入术(Cath)的问题。此类患者的冠状动脉介入治疗通常会导致血运重建。尽管CORAGE和BARI 2D在负荷测试中包括了广泛的心肌缺血严重程度，但大多数患者都有轻到中度的心肌缺血。观察数据表明，中-重度缺血患者的血运重建与较低的死亡和心肌梗死的可能性有关；这在缺血程度较轻的患者中没有观察到。只有大约一半的中-重度缺血患者需要进行冠状动脉介入治疗。在现代医学治疗(特别是大剂量他汀类药物和抗血小板治疗)的时代，导管和血管重建术的使用率是否适合于最佳的患者管理尚不清楚。这个问题不能用现有的数据解决，因为以前的SIHD临床试验在CATH后招募了患者，在这一点上，基于冠状动脉解剖的入选存在很大的选择偏差。考虑到血运重建有可能提高存活率和减少心脏事件，以及与侵入性管理相关的巨额费用和风险，确定侵入性策略的作用至关重要。界定这一角色是美国比较有效性研究的100大优先事项之一。 拟议的缺血试验将是一项前瞻性、多中心、国际、随机、对照试验，将直接满足SIHD患者对侵入性策略--导管和血管重建--的需求。在400多个部位进行负荷成像后，共有8000名中重度缺血和左心室射血分数为35%的患者入选。基于排除显著左主干病变的需要，符合资格标准的患者将接受盲法冠状动脉CT血管造影术。患者将被随机分到侵入组，如果可行，将接受常规的血管重建和OMT，或者只接受OMT的组。

DESCRIPTION (provided by applicant): The long-term objective of the proposed trial, International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA), is to define the role of an invasive approach in patients with stable ischemic heart disease (SIHD) and substantial ischemia. The trial hypothesis is that cardiac catheterization followed by complete revascularization plus optimal medical therapy (OMT) is superior to OMT alone as the management strategy for patients with moderate-severe ischemia on stress imaging. The primary endpoint will be time to cardiovascular death, myocardial infarction (MI), or hospitalization for unstable angina, resuscitated cardiac arrest, or heart failure. The hypothesis that the invasive strategy will improve quality of life will also be tested. Cost-effectiveness will be assessed. The COURAGE and BARI 2D trials found that an initial management strategy of coronary revascularization did not reduce the risk of death or MI compared with OMT alone in SIHD patients selected on the basis of coronary anatomy. These data raise the question whether cardiac catheterization (cath) is required in stable patients. Cath in such patients usually leads to revascularization. Although COURAGE and BARI 2D included a broad range of severity of myocardial ischemia on stress testing, most patients had mild-moderate ischemia. Observational data suggest that revascularization of patients with moderate-severe ischemia is associated with a lower likelihood of death and MI; this is not observed in patients with lesser degrees of ischemia. Only about half of patients with moderate-severe ischemia are referred for cath. It is unknown whether use rates for cath and revascularization are appropriate for optimal patient management in the era of modern medical therapy (particularly with high dose statins and antiplatelet therapy). This issue cannot be resolved using available data because prior clinical trials in SIHD have enrolled patients after cath, at which point there is substantial selection bias for enrollment based on coronary anatomy. Given the potential for improved survival and fewer cardiac events as a result of revascularization and the significant expense and risks associated with invasive management, the role of an invasive strategy is critically important to define. Defining that role is among the top 100 US priorities for comparative effectiveness research. The proposed ISCHEMIA trial will be a prospective, multicenter, international, randomized, controlled trial that will directly address the need for an invasive strategy-cath and revascularization-in patients with SIHD. A total of 8,000 patients with moderate-severe ischemia and left ventricular ejection fraction >35% will be enrolled after stress imaging from more than 400 sites. Based on the need to exclude significant left main coronary artery disease, patients who meet eligibility criteria will undergo blinded coronary CT angiography. Patients will be randomized to an invasive group that will undergo routine cath with optimal revascularization, if feasible, plus OMT or to a group that receives OMT alone.