CREST is a randomized trial with blinded endpoint adjudication.8
The protocol was approved by all appropriate institutional review boards, and written informed consent was provided by all participants. Enrollment was carried out at 117 CREST centers, and participants could not be randomized until operators had been selected at each site through a validated selection process (CEA),9
or a training and credentialing program (CAS).10
To be eligible, symptomatic patients had to have had a transient ischemic attack, amaurosis fugax, or minor nondisabling stroke in the distribution of the study artery within 180 days of randomization and had to have carotid artery stenosis ≥50% by angiography, ≥70% by ultrasound, or ≥70% by CT angiography or MR angiography if ultrasound was 50% to 69%. Asymptomatic patients had to have carotid artery stenosis of ≥60% by angiography, ≥70% by ultrasound, or ≥80% by CT angiography or MR angiography if ultrasound was 50% to 69%. Patients were not eligible if they had a previous disabling stroke or had chronic atrial fibrillation. Complete eligibility criteria have been reported.8
CAS was performed with the use of the RX Acculink® stent; the RX Accunet® embolic protection device was required except when not technically feasible. For both CAS and CEA, antiplatelet therapy was required before and after the procedure.
The National Institutes of Health (NIH) Stroke Scale (NIHSS), modified Rankin scale, Transient Ischemic Attack (TIA) Stroke Questionnaire, cardiac enzymes, electrocardiogram (ECG), and carotid ultrasound were performed at baseline. Cardiac enzymes were obtained 6–8 hours post-procedure; repeat neurological evaluation, NIHSS, and TIA/Stroke Questionnaire were performed at 18–54 hours; and an ECG was obtained at 6–48 hours and at 1 month. The NIHSS, modified Rankin scale, and carotid ultrasound were also performed at 1, 6, and 12 months and annually thereafter.8
A telephone follow-up call was performed at 3 months and every 6 months thereafter. The Medical Outcomes Study 36-item Short Form Instrument (SF-36) was obtained at baseline, 2 weeks and 1 month post-procedure, and 1 year after randomization.11, 12
The primary endpoint was the occurrence of any stroke, myocardial infarction (MI), or death during the periprocedural period or ipsilateral stroke thereafter up to 4 years. Stroke was defined as an acute neurological event with focal symptoms and signs lasting ≥ 24 hours consistent with focal cerebral ischemia. MI was defined as elevation of cardiac enzymes (CK-MB or troponin) to a value ≥ twice the upper limit of normal for the local center laboratory, plus either the occurrence of chest pain or equivalent symptoms consistent with myocardial ischemia, or ECG evidence of ischemia including new ST segment depression or elevation > 1 mm in ≥ 2 contiguous leads (as determined by the centralized core laboratory).13
Analysis was intention-to-treat. Proportional hazards analysis adjusting for age, sex, and symptomatic status was used to test for treatment differences.
Secondary aims were analyzed by including interaction terms in the proportional hazards models.