STICHES

描述（由申请人提供）：2007年5月，STICH心肌血运重建术假说完成了1212名受试者的入组，其中负责的医生对心肌血运重建术的益处保持平衡。患者按1:1的比例随机分配到有或没有CABG的持续最佳药物治疗（MED）组。在这个固定的样本量下，大约400名患者需要达到全因死亡率的主要终点，以达到90%的功率来检验CABG是否导致假设的死亡率比MED降低25%。存活的STICH受试者将返回进行最后一次访问，平均随访5年，所有调查地点将根据协议在2010年底停止患者随访活动。随后将关闭数据库，解除调查人员的盲目性，并报告5年的结果。STICH受试者代表了第一个LVSD的CAD队列，随机分配到单独药物治疗或并发冠状动脉血运重建术的策略，将开始填补这些高风险患者存在的深刻知识空白。随机分组后，他们接受了由5个核心实验室监督的一系列基线和随访测试，包括ECHO、RN心肌灌注和活力、CMR、神经激素、细胞因子和遗传血液测试（NCG）以及经济和生活质量（EQoL）。我们建议利用幸存的STICH患者提供给医学界的机会，并对这些患者进行额外的5年随访。因此，我们将获得接受最佳药物治疗（MED）合并冠脉搭桥（CABG）和不接受最佳药物治疗（CABG）的HF和LVSD患者至关重要的长期（平均10年）信息。这项STICH扩展研究（在提案中称为STICHES）将利用一个独特且已经非常明确的适合冠脉搭桥的LVSD、HF和CAD患者队列来解决以下具体目标：确定CABG联合MED是否比单独MED能提高10年生存率，以及5年治疗相关的结果差异如何随时间变化。2. 在基线临床状态、症状、冠状动脉解剖、功能状态、无创心肌缺血和生存能力测量和/或基因型定义的重要亚组中，确定CABG合并MED是否会导致健康结果的差异，包括功能状态和症状。3. 量化基线无创心脏成像对长期治疗依赖结果的相对增量预测价值（相对于短期和中期）。4. 确定CABG合并MED与单独MED相比是否会导致心脏形态学、功能和血流动力学随时间（4个月和24个月）的变化，并确定这些变化与10年健康结果的关系。

DESCRIPTION (provided by applicant): The STICH Myocardial Revascularization Hypothesis completed enrollment of 1212 subjects in whom the responsible physicians were at equipoise regarding the benefits of myocardial revascularization in May 2007. Patients were randomized 1:1 to continuing optimal medical therapy (MED) with or without CABG. With this fixed sample size, approximately 400 patients need to meet the primary endpoint of all-cause mortality to achieve 90% power to test whether CABG leads to the hypothesized mortality reduction of 25% over MED. Surviving STICH subjects will return for a final visit with an average follow-up of 5 years and all investigative sites will cease patient follow-up activities by the end of 2010 as per protocol. Database closure, un-blinding of investigators and the reporting of 5 year results will follow subsequently. STICH subjects represent the first ever CAD cohort with LVSD randomized to a strategy of medical therapy alone or with concurrent coronary revascularization and will begin to fill a deep knowledge gap which exists for these high-risk patients. Upon randomization, they underwent a battery of baseline and follow-up testing overseen by 5 core laboratories for ECHO, RN myocardial perfusion and viability, CMR, neurohormonal, cytokine and genetic blood testing (NCG), and economics and quality of life (EQoL). We propose to take advantage of the opportunities that the surviving STICH patients present to the medical community and follow these patients for an additional 5 years. We will thereby acquire critically important longer-term (10-year average) information on patients with HF and LVSD treated with optimal medical therapy (MED) with and without coronary bypass graft (CABG). This STICH Extension Study (referred to in the proposal as STICHES) will capitalize on a unique and already exceptionally well-characterized cohort of patients with LVSD, HF and CAD amenable to CABG to address the following specific aims: 1. To determine whether CABG with MED improves 10 year survival compared to MED alone and how treatment-related outcome differences seen at 5 years vary over time. 2. To determine whether CABG with MED leads to differences in health outcomes including functional status and symptoms compared to MED alone at 10 years among important subgroups defined by baseline clinical status, symptoms, coronary anatomy, functional status, noninvasive measures of myocardial ischemia and viability and/or genotype. 3. To quantify the relative, incremental predictive value of baseline non-invasive cardiac imaging on long-term treatment-dependent results (relative to the short and intermediate-term). 4. To determine whether CABG with MED leads to changes in cardiac morphology, function and hemodynamics over time (4 and 24 months) compared to MED alone and to define how these changes relate to 10 year health outcomes.