The ISCHEMIA Trial - EQOL

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型缺血性心脏病(SIHD)患者中的作用，该研究题为《国际医疗和侵入性方法健康有效性比较研究》。试验假说是，在负荷成像中，对于中到重度缺血的患者，心导管术+完全血运重建术+最佳药物治疗(OMT)作为初始治疗策略优于OMT。主要终点将是心血管死亡、心肌梗死(MI)或因急性心脏事件(不稳定心绞痛、复苏心脏骤停或心力衰竭)住院的时间。我们还将检验侵入性策略将改善生活质量的假设。将对成本效益进行评估。 CORAGE和Bari-2D试验发现，当根据冠状动脉解剖选择患者时，与单纯OMT相比，冠状动脉再血管化的初始管理策略并不能降低SIHD患者的死亡或心肌梗死风险。这些数据提示，在病情稳定的患者中可能不需要进行心脏插管(Cath)。此类患者的冠状动脉介入治疗通常会导致血运重建。COURAGE和BARI-2D在激励性测试中包括了大范围的心肌缺血严重程度；大多数患者都有轻到中度的缺血。然而，观察数据表明，在中到重度缺血的患者中，血管重建与较低的死亡和MI的可能性有关，而在缺血程度较轻的患者中则不相关。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。目前尚不清楚在现代医学治疗(大剂量他汀类药物和抗血小板治疗)时代，导管和血管重建术的使用率是否适合最佳的患者管理。这个问题不能用现有的数据解决，因为以前在SIHD进行的临床试验在CATH后招募了患者，在这一点上，基于解剖学的招募存在很大的选择偏差。考虑到血运重建延长生命和避免不良临床心脏事件的可能性，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。 拟议的缺血试验将是一项前瞻性、多中心、国际化、随机对照试验，将直接满足SIHD患者对侵入性策略、介入治疗和血运重建的需求。我们计划从400-500个中重度缺血和左心室射血分数为35%的部位招募大约8,000名患者，这些患者是在负荷成像后招募的。符合资格标准的患者将接受盲法冠状动脉CT血管造影术，以排除显著的左冠状动脉主干疾病和非梗阻性疾病。随机分为侵入组的患者将按照研究指南进行最佳的血管重建。

DESCRIPTION (provided by applicant): The long-term objective of the proposed trial, entitled 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). The trial hypothesis is that cardiac catheterization followed by complete revascularization plus optimal medical therapy (OMT) is superior to OMT alone as the strategy for initial management of patients with moderate-to-severe ischemia on stress imaging. The primary endpoint will be time to cardiovascular death, myocardial infarction (MI), or hospitalization for an acute cardiac event (unstable angina, resuscitated cardiac arrest, or heart failure). We will also test the hypothesis that the invasive strategy will improve quality of life. 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 in SIHD compared with OMT alone when patients were selected based on coronary anatomy. These data have prompted inference that cardiac catheterization (cath) may not be required in stable patients. Cath in such patients usually leads to revascularization. COURAGE and BARI-2D included a broad range of severity of myocardial ischemia on provocative testing; most patients had mild-moderate ischemia. However, observational data suggest that revascularization is associated with a lower likelihood of death and MI in patients with moderate-severe ischemia but not 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 (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 anatomy. Given the potential for extension of life and avoidance of adverse clinical 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. 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. We plan to enroll approximately 8,000 patients from among 400-500 sites with moderate-severe ischemia and left ventricular ejection fraction >35% who are recruited after stress imaging. Patients who meet eligibility criteria will undergo blinded coronary CT angiography to exclude significant left main coronary artery disease and nonobstructive disease. Patients randomized to the invasive group will undergo optimal revascularization following study guidelines.