Revascularization of Asymptomatic Carotid Artery Stenosis

Importance: Studies show that asymptomatic carotid artery stenosis is associated with diminished cognition. Whether carotid revascularization leads to cognitive improvement is unclear. Objective: To determine whether carotid revascularization improves cognition. Design, Setting, and Participants: Prespecified cognitive secondary outcomes of the CREST-2 randomized clinical trials of patients 35 years or older with 70% or greater asymptomatic carotid stenosis. Enrollment was December 2014 through July 2024, and follow-up ended July 2025. Five cognitive tests were administered before treatment and annually up to 4 years. Cognitive performances from 146 clinical sites were centrally assessed by telephone, blinded to treatment. Interventions: Two trials compared carotid stenting plus intensive medical management (CAS + IMM) with IMM alone and carotid endarterectomy plus IMM (CEA + IMM) with IMM alone. Main Outcomes and Measures: Five cognitive tests, assessing learning, memory, executive function, attention, and processing speed, administered to all patients, were assessed for unadjusted and adjusted mean z scores using a linear mixed model. The minimal clinically important difference was 0.50 SD between treatment groups. The prespecified primary analysis was the fully adjusted composite z score at 4 years. Secondary analyses assessed the individual tests and at the test intervals. Results: Among 2366 US study patients, 2165 (91.5%) participated in cognitive assessments, 1078 in the CAS trial (529 CAS + IMM; 549 IMM alone) and 1087 in the CEA trial (543 CEA + IMM; 544 IMM alone); mean age was 70.1 years (SD, 7.7) and 37.8% were female. Following baseline, 4954 test batteries were administered for a mean of 2.24 (SD, 1.09) follow-up years. There were no treatment-related differences in the fully adjusted estimated composite z scores at 4 years for either the CAS trial (CAS + IMM, 0.22 [95% CI, 0.13 to 0.30] vs IMM alone, 0.18 [95% CI, 0.09 to 0.27]; between-group difference, 0.03 [95% CI, -0.09 to 0.15]) or the CEA trial (CEA + IMM, 0.25 [95% CI, 0.17 to 0.33] vs IMM, 0.23 [95% CI, 0.15 to 0.32]; between-group difference, 0.02 [95% CI, -0.09 to 0.14]). There were no significant differences between revascularization plus medical management vs IMM alone for any individual cognitive test. Conclusions and Relevance: In patients with severe asymptomatic carotid artery stenosis, revascularization with either CAS or CEA plus IMM, compared with IMM alone, did not significantly improve cognitive function at up to 4 years of follow-up.