Plaque morphologic characteristics that affect prevention of stroke by carotid revascularization

/ABSTRACT Disruption of carotid atherosclerotic plaque can cause atheroembolism and ischemic stroke. Treating the plaque with surgery or stenting reduces the long-term risk of atheroembolism but with an upfront risk of causing stroke during the revascularization procedure. Compelling evidence supports a net benefit from revascularization in patients with symptomatic carotid stenosis. However, there is a clinical need to improve selection of patients with asymptomatic high-grade (≥70% luminal reduction) carotid stenosis for endarterectomy or stenting in the context of modern intensive medical management (IMM) of atherosclerosis risk factors. CREST-2 (NCT02089217) is a pair of multicenter, randomized trials of IMM with or without revascularization for preventing stroke in patients with high-grade asymptomatic carotid stenosis. CREST-2 completed enrollment of 2,480 patients. Trial follow-up ends on July 31, 2025. CREST-2 specifies baseline pre-randomization carotid duplex ultrasound (DUS) and annual follow-up studies. DUS studies are performed at a lab trained by the CREST-2 Vascular Imaging Core (VIC). DUS blood flow measurements are used to confirm degree of carotid stenosis. The DUS studies also generate standardized B-mode images depicting carotid plaque. The VIC has archived these images. Using standardized image analysis algorithms on the first 503 trial DUS studies, we have successfully assessed the plaque morphologic characteristics we plan to study in this proposal. We will analyze 2000 baseline CREST-2 DUS images of the randomized artery and evaluate relationships between baseline plaque morphologic traits and periprocedural stroke or death plus subsequent ipsilateral stroke. We will also characterize the effectiveness of IMM in changing DUS plaque morphologic features over time in 500 patients followed longitudinally (1000 arteries total: 500 arteries on the randomized side along with 500 arteries on the contralateral side). The directed approach we propose overcomes difficulties inherent in non-randomized cohort studies, including observer bias and confounding by indication. This proposal will, for the first time in a multicenter randomized trial, determine the clinical utility of assessing morphological traits for selecting asymptomatic patients for revascularization and testing new therapies. Project Number: 1R01NS147997-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator: JAMES MESCHIA (+2 co-PIs) | Institution: MAYO CLINIC JACKSONVILLE, JACKSONVILLE, FL | Award Amount: $442,086 | Activity Code: R01 | Study Section: Special Emphasis Panel[ZRG1 CN-A (81)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11337818