The ISCHEMIA Trial - SDCC

描述（由申请人提供）： 拟议试验的长期目标，医疗和侵入性方法（ISCHEMIA）比较健康效果的国际研究，是确定侵入性方法在稳定性缺血性心脏病（SIHD）和严重缺血患者中的作用。试验假设是，心脏导管插入术后完全血运重建加最佳药物治疗（OMT）上级OMT单独作为患者的管理策略与中重度缺血负荷成像。主要终点是至心血管死亡、心肌梗死（MI）或因不稳定型心绞痛住院、心脏骤停复苏或心力衰竭的时间。还将检验侵入性策略将改善生活质量的假设。将评估成本效益。 COUHD和巴里2D试验发现，在根据冠状动脉解剖结构选择的SIHD患者中，与单独OMT相比，冠状动脉血运重建的初始管理策略并未降低死亡或MI的风险。这些数据提出了一个问题，即稳定的患者是否需要心导管插入术。导管在这类患者中通常导致血运重建。虽然COURANT和巴里2D包括负荷试验中广泛的心肌缺血严重程度，但大多数患者存在轻度-中度缺血。观察数据表明，中重度缺血患者的血运重建与死亡和MI的可能性较低相关;在缺血程度较轻的患者中未观察到这一点。只有大约一半的中重度缺血患者被转诊接受导管插入术。目前尚不清楚在现代医学治疗（特别是高剂量他汀类药物和抗血小板治疗）时代，导管插入和血运重建的使用率是否适合于最佳患者管理。使用现有数据无法解决该问题，因为SIHD的既往临床试验已入组导管插入术后患者，此时基于冠状动脉解剖结构的入组存在显著的选择偏倚。考虑到血运重建可能提高生存率和减少心脏事件，以及与侵入性管理相关的重大费用和风险，确定侵入性策略的作用至关重要。确定这一角色是美国比较有效性研究的100个优先事项之一。 拟定的ISCHEMIA试验将是一项前瞻性、多中心、国际、随机、对照试验，将直接解决SIHD患者对侵入性策略-导管插入术和血运重建术的需求。在400多个站点进行负荷成像后，共将入组8,000例中重度缺血且左心室射血分数>35%的患者。基于排除显著左主干冠状动脉疾病的需要，符合合格标准的患者将接受设盲冠状动脉CT血管造影。患者将被随机分配到侵入性组，该组将接受常规导管术和最佳血运重建（如果可行），加上OMT，或接受OMT单独治疗。

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.