Computed-Tomography Angiography-Based Carotid Plaque-RADS, Recurrent Vascular Events, and the Effect of Colchicine: An Imaging Substudy of the CONVINCE Randomized Trial

BACKGROUND: The carotid Plaque Reporting and Data System (Plaque-RADS) provides a standardized framework for evaluating plaque morphology, but prospective validation remains limited. We investigated the association between computed tomography angiography-based Plaque-RADS categories and subsequent ischemic events in patients with noncardioembolic stroke/transient ischemic attack, from a completed clinical trial of colchicine. Second, we assessed whether the effect of colchicine differed by Plaque-RADS risk classification. METHODS: We conducted a posthoc observational cohort analysis of 517 participants in the CONVINCE trial (Colchicine for Prevention of Vascular Inflammation in Non-CardioEmbolic Stroke) from 13 European sites. Associations between Plaque-RADS and recurrent ipsilateral stroke, any stroke/transient ischemic attack, and major adverse cardiovascular events were assessed using multivariable Cox proportional hazards models. Plaque-RADS was analyzed as both dichotomized (<3 versus ≥3) and ordinal (per 1-point increase) variables. Treatment effects were assessed by Plaque-RADS classification using interaction and stratified analyses. RESULTS: A total of 510 patients (median age, 67.0 years; 72.2% male) with 966 internal carotid arteries were included. Among 321 internal carotid arteries ipsilateral to the index ischemic stroke, 12 recurrent ipsilateral strokes, 32 any strokes/transient ischemic attacks, and 37 major adverse cardiovascular events occurred over a median 35.7-month follow-up. Plaque-RADS ≥3 (n=140) was independently associated with recurrent ipsilateral stroke (adjusted hazard ratio, 7.80 [95% CI, 1.55–39.30]; P =0.01), any stroke/transient ischemic attack (adjusted hazard ratio, 3.94 [95% CI, 1.68–9.24]; P <0.01), and major adverse cardiovascular events (adjusted hazard ratio, 2.52 [95% CI, 1.19–5.34]; P =0.02) after adjustment for age, sex and cardiovascular risk factors. A significant interaction with colchicine treatment was observed for major adverse cardiovascular events ( P =0.047), with greater benefit among patients with Plaque-RADS scores ≥3 (hazard ratio, 0.35 [95% CI, 0.15–0.82]). CONCLUSIONS: In internal carotid arteries ipsilateral to the index ischemic stroke, computed tomography angiography-based carotid Plaque-RADS was associated with recurrent ischemic stroke and cardiovascular events. Importantly, treatment effects of colchicine varied across Plaque-RADS classification (<3 versus ≥3), suggesting that plaque vulnerability assessment may help refine patient selection for anti-inflammatory therapy beyond stenosis-based classification. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02898610.