CREST-2 Statistical and Data Coordinating Center - SDCC

描述（由申请人提供）：本申请的广泛、长期目标是推进因颈动脉粥样硬化而有卒中风险的患者的卒中一级预防。 4%到8%的成年人有超过50%的无症状颈动脉狭窄。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，每年约有100，000例颈动脉内膜切除术和40，000例颈动脉支架植入术。高达90%的此类手术是在无症状患者身上进行的。药物治疗有所改善。ACST试验表明，高脂血症的药物治疗会削弱无症状狭窄患者血运重建的益处。动脉粥样硬化危险因素管理的进一步进展可能会抵消通过血运重建可能实现的获益，从而使手术的发病率变得不合理。动脉内膜切除术和支架植入术也有所改善。CREST的动脉内膜切除术结果显示围手术期卒中和死亡率为1.4%。对于支架植入术，这一比率是随机对照试验中报告的最低水平，为2.5%，并且在最后三分之一的入组中该比率正在提高。 我们将进行两项平行随机、多中心非劣效性试验（CREST-2）。主要具体目的是比较强化医疗管理与颈动脉内膜切除术（n=1050）的有效性，以及比较强化医疗管理与支架植入术（n=1050）对高度无症状颈动脉狭窄患者的有效性。主要终点将是随机化30天内的任何卒中或死亡加上随访4年的同侧卒中的复合终点。血管危险因素， 包括高血压、糖尿病、吸烟和高脂血症，将使用现代积极目标进行集中管理。如果强化医疗管理被宣布为不劣于动脉内膜切除术、支架植入术或两者，则可以预防多达5，000例围手术期卒中。

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.