The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial EXTENDed Follow-up (EXTEND)

项目摘要/摘要 医学方法和侵入性方法健康效果比较的国际研究 (缺血)延长随访(EXTEND)是对随机、存活的参与者的长期随访 在缺血状态下。这项由NHLBI支持的试验随机选择了5,179名患有稳定型缺血性心脏病的患者 两种不同的管理策略：1)心导管的初始有创策略(INV)和 可行的血运重建加以指南为基础的药物治疗(GBMT)，或2)最初的保守治疗 GBMT战略。这项试验没有显示初始有创手术的主要终点的减少 策略。围手术期心肌梗死(MI)增多，自发性MI减少 在INV组。先前的证据表明，自发性心肌梗死具有更高的后续死亡风险 而不是围手术期心肌梗死。在心血管(CV)死亡率曲线上有一个较晚的分离，超过一年 缺血的中位随访时间为3.2年。INV策略对MI率的总体降低并没有 直到两年后才会出现。因此，基于观察到的自发MI的减少，迫切需要 确定长期生命状态，为患者和临床医生提供关于INV策略是否有效的有力证据 从长远来看，减少简历和各种原因造成的死亡。预计有728例心血管疾病死亡(总计1000例) 有足够的功率来检测组之间的差异。同样重要的是，提高 点估计以排除福利(如果不存在)。不管研究结果如何，稳健的长期死亡率 数据对临床指南和实践具有巨大的影响，正如独立专家所确认的那样， 撰写和监督国家指导方针的制定，以及谁提供了支持信。我们还将 量化非致命性心血管事件对缺血后死亡率的影响-扩展，构建风险 使用基线深层表型数据对死亡率进行评分，并提供对INV在 最高风险亚组-那些患有严重冠状动脉疾病的人，目前的实践指南 推荐冠状动脉搭桥术(CABG)以提高存活率。我们已经获得了所有必要的批准和 99%的人同意。我们准备对99%的人进行更长时间的死亡跟踪，包括死亡原因 存活的参与者获得了10年的中位随访期。我们将通过参与者/代理来确定重要状态 每6个月通过电话或电子邮件联系，或通过搜索高质量的国家/地区健康/死亡 数据库。参与者最后一次联系日期、死亡日期、死因和信息来源 收集并输入以网络为基础的电子数据采集系统。我们优秀的参与者留存率， 在最初的试验阶段和我们的后续试验阶段遵守协议、数据完整性和质量 在获得所需批准和同意的情况下，取得了进展，确保了这项研究将实现其目标的信心。

PROJECT SUMMARY/ ABSTRACT The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) EXTENDed Follow-up (EXTEND) is the long-term follow-up of randomized, surviving participants in ISCHEMIA. This NHLBI-supported trial randomized 5,179 participants with stable ischemic heart disease to two different management strategies: 1) an initial invasive strategy (INV) of cardiac catheterization and revascularization when feasible plus guidelines-based medical therapy (GBMT), or 2) an initial conservative strategy of GBMT. The trial did not demonstrate a reduction in the primary endpoint with an initial invasive strategy. There was an excess of peri-procedural myocardial infarction (MI) and a reduction in spontaneous MI in the INV group. Prior evidence demonstrates that spontaneous MI carries a higher risk of subsequent death than peri-procedural MI. There was a late separation in the cardiovascular (CV) mortality curves, over a median of 3.2 years follow-up in ISCHEMIA. The overall reduction in MI rates with an INV strategy did not emerge until after 2 years. Therefore, based on the observed reduction in spontaneous MI, it is imperative to ascertain long-term vital status to provide patients and clinicians with robust evidence on whether INV strategy reduces CV and all-cause death over the long-term. With projected 728 CV deaths (1000 total) we have adequate power to detect a between group difference. It is equally important to improve precision around the point estimate to rule out a benefit if none exists. Regardless of the study findings, robust long-term mortality data have enormous implications for clinical guidelines and practice, as affirmed by independent experts who write and oversee the development of national guidelines, and who provided letters of support. We will also quantify the impact of nonfatal CV events on subsequent mortality in ISCHEMIA-EXTEND, construct a risk score for mortality using baseline deep phenotypic data, and provide estimates of the impact of INV in the highest risk subgroup – those with severe coronary artery disease for whom current practice guidelines recommend coronary artery bypass (CABG) to improve survival. We have obtained all required approvals and 99% of consents. We are ready to conduct extended follow-up of death, including cause of death, on >99% of surviving participants resulting in 10-year median follow-up. We will ascertain vital status by participant/proxy contact every 6 months via telephone or email, or by searching high-quality national/regional health/death databases. Participant last contact date, date of death, cause of death, and source of information will be collected and entered into a web-based electronic data capture system. Our excellent participant retention, adherence to protocol, data completeness and quality during the initial trial phase, and our subsequent progress, with required approvals and consents secured, assure confidence that the study will meet its goals.