Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial - Hemodynamics (CREST-H)

高度颈动脉狭窄引起的脑血流动力学损害可损害认知功能 即使在没有中风的情况下，也会直接或间接导致认知能力下降， 无症状性梗死的发生率更高虽然有良好的初步证据，从案件 血流动力学损害影响认知功能的系列和生理学研究 颈动脉闭塞性疾病，这种疾病的治疗从未在随机临床试验中进行过测试。 审判我们建议对NINDS赞助的CREST-2试验进行一项辅助研究，这是一对 无症状高分级颈动脉患者的结局设盲、III期临床试验 狭窄，将比较颈动脉内膜切除术加最佳药物治疗（OMT）与 OMT单独治疗（n= 1，240），颈动脉支架植入术+OMT与OMT单独治疗（n= 1，240），以预防 中风和死亡.我们的应用程序解决了一个有趣的问题， 当损伤是由脑血流动力学灌注异常引起时， CREST-2随机化患者的血流动力学受损亚组。我们将招收500名 来自CREST-2的患者，所有患者均在基线和每年接受认知评估 然后我们将确定100例血流动力学受损的患者， 狭窄侧半球MRI灌注“达峰时间”（TTP）延迟。的人中 被发现血流动力学受损，并有基线认知障碍，认知功能 基线和1年时的电池将确定是否有血流衰竭的患者被分配到 CREST-2中的血运重建组的认知结局优于医疗组， 仅手臂与此治疗组相比有差异者无血流衰竭。我们 假设血流动力学上显著“无症状”颈动脉疾病可能代表 几个可以治疗的认知障碍的例子。如果认知能力下降可以逆转 在这些患者中，我们将建立一个新的颈动脉血运重建的适应症， 独立于复发性中风的风险。

Cerebral hemodynamic impairment due to high-grade carotid artery stenosis can impair cognition even in the absence of stroke, contributing to cognitive decline either directly, or as a consequence of a higher occurrence of silent infarction. Although there is good preliminary evidence from case series and physiological studies that hemodynamic impairment affects cognition in patients with carotid occlusive disease, treatment of this condition has never been tested in a randomized clinical trial. We propose to conduct an ancillary study to the NINDS-sponsored CREST-2 trial, a pair of outcome-blinded, Phase 3 clinical trials for patients with asymptomatic high-grade carotid artery stenosis which will compare carotid endarterectomy plus optimal medical therapy (OMT) versus OMT alone (n=1,240), and carotid artery stenting plus OMT versus OMT alone (n=1,240) to prevent stroke and death. . Our application addresses the intriguing question of whether cognitive impairment can be reversed when it arises from abnormal cerebral hemodynamic perfusion in a hemodynamically impaired subset of the CREST-2 –randomized patients. We will enroll 500 patients from CREST-2, all of whom receive cognitive assessments at baseline and yearly thereafter. We will identify 100 patients with hemodynamic impairment as measured by an inter- hemispheral MRI perfusion “time to peak” (TTP) delay on the side of stenosis. Among those who are found to be hemodynamically impaired and have baseline cognitive impairment, the cognitive batteries at baseline and at 1 year will determine if those with flow failure who are assigned to revascularization arm in CREST-2 will have better cognitive outcomes than those in the medical- only arm compared with this treatment difference for those who have no flow failure. We hypothesize that hemodynamically significant “asymptomatic” carotid disease may represent one of the few examples of treatable causes of cognitive impairment. If cognitive decline can be reversed in these patients, then we will have established a new indication for carotid revascularization independent of the risk of recurrent stroke.