Revascularization of Asymptomatic Carotid Artery Stenosis: Cognitive Results of the CREST-2 Randomized Trials.

Abstract

Studies show that asymptomatic carotid artery stenosis is associated with diminished cognition. Whether carotid revascularization leads to cognitive improvement is unclear. To determine whether carotid revascularization improves cognition. 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. Two trials compared carotid stenting plus intensive medical management (CAS + IMM) with IMM alone and carotid endarterectomy plus IMM (CEA + IMM) with IMM alone. 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. 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. 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.