STICHES

描述(由申请人提供)：STICH心肌血管重建术假说于2007年5月完成了1212名受试者的登记，在这些受试者中，负责的医生对心肌血管重建术的益处持平衡态度。患者被随机分为1：1继续最佳内科治疗(MED)组和非CABG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，才能达到90%的能力来测试CABG是否导致假设的死亡率比MED降低25%。幸存的STICH受试者将返回进行最后一次访问，平均随访时间为5年，根据协议，所有调查地点将在2010年底之前停止患者随访活动。随后将关闭数据库，解除调查人员的盲目，并报告5年结果。STICH受试者是有史以来第一个有LVSD的冠心病队列，他们被随机分成单独的药物治疗策略或同时进行冠状动脉血管重建的策略，并将开始填补对这些高危患者存在的深层次知识空白。在随机分组后，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心肌灌注和存活率、CMR、神经激素、细胞因子和遗传血液测试(NCG)以及经济学和生活质量(EQOL)。我们建议利用存活的STICH患者为医学界提供的机会，并对这些患者再跟踪5年。因此，我们将获得关于接受最佳药物治疗(MED)和非冠脉搭桥术(CABG)的HF和LVSD患者的至关重要的长期(10年平均)信息。这项STICH扩展研究(在提案中称为Sitches)将利用一组独特的、已经非常清楚地描述了可以接受冠状动脉旁路移植术的LVSD、HF和CAD患者，以解决以下具体目标：1.确定与MED相比，CABG是否能提高10年存活率，以及5年后与治疗相关的结果差异如何随时间变化。2.通过基线临床状态、症状、冠状动脉解剖、功能状态、心肌缺血的非侵入性测量和存活和/或基因，确定10年后CABG合并MED与单纯MED相比，是否会导致包括功能状态和症状在内的健康结局的差异。3.量化基线无创心脏成像对长期治疗依赖结果(相对于短期和中期)的相对、递增的预测价值。4.确定与单纯MED相比，CABG合并MED是否会导致心脏形态、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。 公共卫生相关性：美国有500多万患者患有心力衰竭，其中大多数患者与冠心病有关。许多患者接受无创和有创的心血管成像，随后进行冠状动脉血运重建，个人和社会都付出了巨大代价。斯蒂克斯研究的结果将有助于指导患者的选择，并更好地告知这些策略是否会为这些高危个人和整个社会带来更好的健康结果。

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. PUBLIC HEALTH RELEVANCE: Over 5 million patients have HF in the Unites States with the majority having associated CAD. Many undergo non-invasive and invasive cardiovascular imaging followed by coronary revascularization at a significant personal and societal cost. The results of the STICHES study will help guide patient selection and better inform whether these strategies lead to better health outcomes for these high-risk individuals and for the society as a whole.