Abstract Body: INTRODUCTION
The Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) will test if carotid endarterectomy (CEA) or carotid stenting (CAS) plus intensive medical therapy (IMT) are superior to IMT alone in preventing stroke in asymptomatic patients with carotid stenosis ≥ 70%. Randomization was carried out at 143 sites in 5 countries and was completed in July 2024. Enrollment criteria for the 2485 patients included degree of stenosis by carotid duplex ultrasound (DUS). Bias toward low-stenosis severity is an important concern in carotid trials, thus we present results of the first 2000 CREST-2 patients analyzed for degree of stenosis.

METHODS
Patients were examined via a standardized DUS protocol at credentialed US labs with images reviewed centrally. Eligibility for enrollment required: 1) a catheter-based angiogram with ≥70% stenosis, or 2) a DUS with a peak systolic velocity (PSV) ≥230cm/sec plus one of the following: end diastolic velocity (EDV) ≥100cm/sec, internal carotid to common carotid velocity ratios (ICA:CCA) ≥ 4, computed tomography or magnetic resonance angiography with ≥70% stenosis. PSV, EDV, and ICA:CCA were measured. A PSV of ≥389 cm/sec was assigned a stenosis of 80-99%, based on velocity criteria from an independent quality control cohort of >8000 patients.

RESULTS
Mean (SD) age of the cohort was 69.8 years (7.8), 37.9% were female, 90.3% were white and 4.5% Hispanic. Vascular risk factors were highly prevalent: 37.8% had diabetes, 92.0% dyslipidemia, and 86.0% hypertension at the time of entry into the trial. The index carotid stenosis was located on the right side (52.3% of patients) more often than the left. The mean PSV was 360.0 cm/sec [interquartile range (286, 422)]. The distribution of the PSVs indicated a wide range of stenosis among the patients randomized (see histogram below). Of the 2000 DUS performed, 684 (34.2%) had a stenosis of 80-99%, and 69% had a PSV >300cm/sec.

CONCLUSION
Methods for enrollment into CREST-2, a pivotal trial comparing CEA or CAS to IMT alone in prevention of stroke, have accomplished randomization of patients with a wide range in the degree of severe carotid stenosis. No bias toward low-stenosis severity is evident in the first 2000 patients randomized, and one third had extremely high-grade, 80-99%, stenosis. The heterogeneity of the severity of stenosis will allow analysis for the possibility of differential treatment effects.