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.

Public Health Relevance

In the United States, more than 100,000 carotid endarterectomy or stent procedures are performed annually on patients with asymptomatic carotid stenosis. Recent advances in medical management of atherosclerotic disease call into question whether the benefit of these procedures in preventing stroke persists. We propose two parallel multicenter randomized clinical trials, one of which will compare intensive medical management to endarterectomy (n=1050) and the other will compare intensive medical management to stenting (n=1050).

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project--Cooperative Agreements (U01)
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National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
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Moy, Claudia S
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University of Alabama Birmingham
Biostatistics & Other Math Sci
Schools of Public Health
United States
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Brott, Thomas G; Meschia, James F; Lal, Brajesh K (2017) Duplex velocity criteria for carotid endarterectomy. J Vasc Surg 65:938-939
Howard, Virginia J; Meschia, James F; Lal, Brajesh K et al. (2017) Carotid revascularization and medical management for asymptomatic carotid stenosis: Protocol of the CREST-2 clinical trials. Int J Stroke 12:770-778
Demaerschalk, Bart M; Brown Jr, Robert D; Roubin, Gary S et al. (2017) Factors Associated With Time to Site Activation, Randomization, and Enrollment Performance in a Stroke Prevention Trial. Stroke 48:2511-2518