Abstract Body: Introduction: Over 100,000 carotid revascularization procedures are done annually in the US for asymptomatic carotid arterial stenosis. The safety of revascularization by carotid endarterectomy (CEA) and carotid stenting (CAS) and the efficacy of medical therapy to reduce risk of stroke related to atherosclerosis have both improved. Therefore, the applicability of prior randomized trials in asymptomatic carotid stenosis to current treatment decisions has been questioned.

Methods: The aim of the NINDS-funded CREST-2 (clincialtrials.gov no. NCT02089217) is to compare CEA and intensive medical management (IMM) versus IMM alone (target n=1240), and CAS and IMM versus IMM alone (target n=1240), through two parallel randomized trials at ~213 medical centers, including collaboration with NIH-StrokeNet. The composite primary outcome is any stroke or death within 44 days after randomization or ipsilateral ischemic stroke thereafter up to 4 years. Secondary outcomes include cognitive function, which is assessed on a regular schedule through computer-assisted telephone interviews. IMM is directed centrally and includes tight control of blood pressure (systolic target <130 mm Hg) and cholesterol (LDL target < 70 mg/dl) as well as lifestyle coaching.

Results: Recruitment was completed on July 11, 2024, with a total of 2485 patients enrolled across 155 sites. Follow-up ended for the CEA and IMM vs. IMM trial on September 30, 2024. Follow-up is expected to end for the CAS and IMM vs. IMM trial on July 31, 2025. Mean age of trial participants was 70, and 37% (926/2485) were female. 92% (2286/2485) were enrolled at U.S. centers and the remainder across 4 countries. A post-trial observational study is ongoing at participating centers to surveil for late post-procedural stroke endpoints.

Conclusion: CREST-2 is designed to identify the best approach to stroke prevention for asymptomatic carotid stenosis. The recruitment goals were achieved in July, 2024. An update will be provided regarding patient characteristics including basic demographic data.