CREST-2 Statistical and Data Coordinating Center - SDCC

描述(由申请人提供)：这项申请的广泛、长期目标是在由于颈动脉粥样硬化而有中风风险的患者中推进中风的一级预防。4%至8%的成年人无症状颈动脉狭窄超过50%。颈动脉狭窄通常通过动脉内膜切除术或支架置入术来治疗。在美国，每年大约有10万例颈动脉内膜切除术和4万例颈动脉支架手术。高达90%的这些手术是在没有症状的患者身上进行的。医学治疗有了进步。ACST试验表明，对高脂血症的内科治疗可以削弱无症状狭窄患者血管重建的益处。动脉粥样硬化危险因素管理的进一步进展可能会抵消原本可能通过血运重建实现的好处，使手术的发病率变得不合理。动脉内膜切除术和支架置入术也有所改善。CREST动脉内膜剥脱术围手术期发生卒中，死亡率为1.4%。对于支架植入，这是随机对照试验中报道的最低比率，为2.5%，而且在登记的最后一季度，这一比率正在改善。我们将进行两个平行的随机多中心非劣势试验(CREST-2)。主要的具体目标将是比较强化医疗管理与颈动脉内膜切除术(n=1050)的有效性，以及比较高度无症状颈动脉狭窄患者强化医疗管理与支架置入术(n=1050)的有效性。主要终点将是随机化30天内的任何中风或死亡加上长达4年的随访的同侧中风。血管危险因素， 包括高血压、糖尿病、吸烟和高脂血症在内的疾病将使用现代积极的目标进行集中管理。如果宣布强化医疗管理不逊于动脉内膜切除术、支架置入术或两者兼而有之，则可预防多达5000例围手术期中风。

DESCRIPTION (provided by applicant): The broad, long-term objective of this application is to advance primary prevention of stroke in patients at risk for stroke due to atherosclerosis of the carotid artery. Four to eight percent of adults have asymptomatic carotid stenosis exceeding 50%. Carotid stenosis is often managed either by endarterectomy or stenting. About 100,000 carotid endarterectomies and 40,000 carotid stenting procedures are done each year in the US. Up to 90% of these procedures are done on asymptomatic patients. Medical therapy has improved. The ACST trial demonstrated that medical management of hyperlipidemia can attenuate the benefits of revascularization in patients with asymptomatic stenosis. Further advances in managing atherosclerotic risk factors may negate benefit that might otherwise be realized through revascularization, making the morbidity of the procedures unjustifiable. Endarterectomy and stenting have also improved. The results for endarterectomy in CREST showed a periprocedural stroke and death rate of 1.4%. For stenting, the rate was the lowest yet reported in a randomized controlled trial, 2.5%, and that rate was improving in the last tertil of enrollment. We will conduct two parallel randomized, multicenter non-inferiority trials (CREST-2). The primary specific aims will be to compare the effectiveness of intensive medical management to carotid endarterectomy (n=1050) and also to compare the effectiveness of intensive medical management to stenting (n=1050) for patients with high-grade asymptomatic carotid artery stenosis. The primary endpoint will be a composite of any stroke or death within 30 days of randomization plus ipsilateral stroke up to 4 years of follow-up. Vascular risk factors, including hypertension, diabetes mellitus, cigarette smoking and hyperlipidemia, will be managed centrally using modern aggressive targets. Should intensive medical management be declared non-inferior to endarterectomy, stenting or both, up to 5,000 periprocedural strokes may be prevented.