CIAO-ISCHEMIA - Resubmission - 1

CIAO-ISCHEMIA - 重新提交 - 1

• 批准号: 8918315
• 负责人: HARMONY R. REYNOLDS
• 金额: $ 44.66万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-28 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8918315
• 关键词: Acetylcholine; Affect; Age; Anatomy; Ancillary Study; Angiography; Arteries; Atherosclerosis; Blood flow; Cardiac Catheterization Procedures; Cardiovascular system; Caring; Cessation of life; Chest Pain; Clinical; Clinical Trials; Collection; Coronary; Coronary Arteriosclerosis; Emergency department visit; Enrollment; Evaluation; Event; Evolution; Failure; Frequencies; Future; General Population; Guidelines; Heart; Heart Diseases; Hospitalization; Image; Ischemia; Laboratories; Link; Measurement; Myocardial Ischemia; Outcome; Pain; Participant; Patients; Pharmaceutical Preparations; Physicians; Population; Process; Questionnaires; Randomized; Recommendation; Recruitment Activity; Research; Risk; Severities; Stenosis; Stress; Stress Echocardiography; Stress Tests; Stroke; Subgroup; Symptoms; Test Result; Testing; Time; Ultrasonography; Vasospasm; Woman; abstracting; cohort; cost; design; follow-up; high risk; interest; life time cost; outcome forecast; public health relevance; randomized trial; sex; symptom management; treatment trial; vascular abnormality

DESCRIPTION (provided by applicant): Patients referred for angiography to evaluate chest pain are frequently found to have no "obstructive" coronary artery disease (CAD), i.e., no angiographic stenosis of e50%. For such patients, the reason for chest pain or other ischemic symptoms may not be clear. Prior research has shown that some patients with symptoms and without obstructive CAD have objective abnormalities that may represent the cause of chest pain, such as ischemia on stress imaging, abnormal coronary flow reserve, acetylcholine-induced vasospasm, or atherosclerosis that is more extensive than appreciated on the angiogram. Each of these objective findings is associated with increased risk of events during follow up, such as death and MI. Despite prior mechanistic research, it remains unclear whether ischemic symptoms are in fact due to myocardial ischemia in some or all patients, because other lines of research have shown abnormal pain sensitivity and processing in patients without obstructive CAD. Further, there has been no well-powered study linking the evolution of symptoms and objective measurement of ischemia over time. There remains the possibility that some patients may have symptoms that are not ischemic in origin, in which case ischemia could be silent or a false positive result. Reflecting this lack of clarity, guideline recommendations are very limited and focus on symptom management. We hypothesize that a) changes in ischemia and angina over time are correlated, because angina is due to ischemia in these patients; b) anti-anginal therapy leads to reduction in angina and ischemia; and c) ischemia and angina are more severe with a greater burden of atherosclerosis. The ISCHEMIA trial is a large randomized trial of a routine invasive vs. conservative strategy for the management of stable CAD with core lab-confirmed moderate-severe ischemia. Participants undergo coronary CT angiography (CCTA) after enrollment and those without obstructive CAD (e50% stenosis) are excluded from randomization. These ISCHEMIA anatomic screen failures represent an ideal population in which to investigate our hypotheses because ischemia will be confirmed by a core laboratory and thus the target cohort should be more likely to have true ischemia. In addition, atherosclerosis will be assessed by a core laboratory in the same patients and the target cohort will already have demonstrated interest in participating in research. Therefore patients can be recruited and additional information obtained with a minimum of extra effort and cost. The CIAO-ISCHEMIA ancillary study will add repeat stress echocardiography and angina assessment at 1 year and collection of events (death, MI, stroke, cardiovascular hospitalizations/ER visits). The primary specific aim is to investigate the association between change in angina severity and change in severity of ischemia of stress echocardiography over one year in patients with an initial finding of moderate-severe ischemia and with no obstructive CAD on CCTA. The association between angina, ischemia and atherosclerosis severity at baseline will be examined. Both sexes will be represented; most prior studies have been restricted to women.

描述（由申请人提供）：转诊进行血管造影以评估胸痛的患者经常被发现没有“阻塞性”冠状动脉疾病（CAD），即没有血管造影狭窄 e50%。对于此类患者，胸痛或其他缺血症状的原因可能尚不清楚。先前的研究表明，一些有症状且无阻塞性 CAD 的患者存在可能导致胸痛的客观异常，例如负荷成像缺血、冠状动脉血流储备异常、乙酰胆碱引起的血管痉挛或比想象的更广泛的动脉粥样硬化在血管造影上。这些客观发现中的每一个都与随访期间事件风险增加相关，例如死亡和心肌梗死。尽管进行了先前的机制研究，但仍不清楚部分或所有患者的缺血症状是否实际上是由心肌缺血引起的，因为其他研究表明，没有阻塞性 CAD 的患者存在异常的疼痛敏感性和处理能力。此外，还没有强有力的研究将症状的演变与缺血随时间的客观测量联系起来。一些患者仍有可能出现非缺血性症状，在这种情况下，缺血可能是无症状的或假阳性结果。指南建议非常有限，并且侧重于症状管理，反映出这种不明确性。我们假设 a) 缺血和心绞痛随时间的变化是相关的，因为这些患者的心绞痛是由缺血引起的； b) 抗心绞痛治疗可减少心绞痛和缺血； c) 缺血和心绞痛更严重，动脉粥样硬化负担更大。 ISCHEMIA 试验是一项大型随机试验，比较常规侵入性策略与保守策略的比较，用于治疗具有核心实验室确认的中重度缺血的稳定型 CAD。参与者在入组后接受冠状动脉 CT 血管造影 (CCTA)，无阻塞性 CAD（e50% 狭窄）的参与者被排除在随机分组之外。这些缺血性解剖筛查失败代表了研究我们假设的理想人群，因为缺血将由核心实验室确认，因此目标人群更有可能患有真正的缺血。此外，动脉粥样硬化将由核心实验室对同一患者进行评估，并且目标人群已经表现出参与研究的兴趣。因此，可以以最少的额外努力和成本招募患者并获得额外信息。 CIAO-ISCHEMIA 辅助研究将增加 1 年重复负荷超声心动图和心绞痛评估以及事件收集（死亡、心肌梗死、中风、心血管住院/急诊室就诊）。主要具体目的是调查一年内首次发现中重度缺血且 CCTA 未发现梗阻性 CAD 的患者心绞痛严重程度变化与负荷超声心动图缺血严重程度变化之间的关联。将检查基线时心绞痛、缺血和动脉粥样硬化严重程度之间的关联。男女都会有代表；大多数先前的研究仅限于女性。