Association of Plaque Inflammation With Stroke Recurrence in Patients With Unproven Benefit From Carotid
Pol Camps-Renom1, John McCabe2, Joan Martí-Fàbregas2
1From the Stroke Unit (P.C.-R., J.M.-F., R.D.-M., M.G.-J., D.G.-A., A.M.-D., L.P.-S.), Department of Neurology, Institute of Biomedical Research Sant Pau (IIB-Sant Pau), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Health Research Board Stroke Clinical Trials Network Ireland (J.M., S.C., E.D., J.A.H., G.H., M.M., S.M., P.J.K.); Neurovascular Clinical Science Unit (J.M., G.H., M.M., S.M., P.J.K.), Stroke Service and Department of Neurology, Mater University Hospital/University College Dublin; Radiography & Diagnostic Imaging (N.G., J.P.M., S.F.), School of Medicine, University College Dublin, Ireland; Discipline of Medical Imaging Science (N.G.), School of Health Sciences, Faculty of Medicine and Health, University of Sydney, Australia; Department of Nuclear Medicine (A.F.-L.), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Department of Neurology (J.-C.B.), Université de Paris, Hopital Sainte-Anne, France; Department of Vascular Surgery (M.B.), St. Vincent's University Hospital and University College Dublin, Ireland; Departments of Clinical Neurosciences, Radiology, and Community Health Sciences (S.B.C.), University of Calgary, Alberta, Canada; Department of Neurology (S.C.), Cork University Hospital; Department of Clinical Neuroscience (S.C.), College of Medicine and Health, University College Cork, Ireland; Connolly Hospital Dublin and Royal College of Surgeons (E.D.); Stroke Service, Department of Geriatric Medicine (J.A.H.), St. James' Hospital and Trinity College; Departments of Radiology (E.C.K., M.O.C.) and Vascular Surgery (C.M.), Mater University Hospital and University College Dublin, Ireland; Division of Neurology (V.K.S.), National University Health System, and Yong Loo Lin School of Medicine, National University of Singapore; and Department of Geriatric and Stroke Medicine (D.W.), RCSI University of Medicine and Health Sciences/Beaumont Hospital, Dublin, Ireland. pcamps@santpau.cat.
Background And Objectives:
In pooled analyses of endarterectomy trials for symptomatic carotid stenosis, several subgroups experienced no net benefit from revascularization. The validated symptomatic carotid atheroma inflammation lumen-stenosis (SCAIL) score includes stenosis severity and inflammation measured by PET and improves the identification of patients with recurrent stroke compared with lumen-stenosis alone. We investigated whether the SCAIL score improves the identification of recurrent stroke in subgroups with uncertain benefit from revascularization in endarterectomy trials.
Methods:
We did an individual-participant data pooled analysis of 3 prospective cohort studies (Dublin Carotid Atherosclerosis Study [DUCASS], 2008-2011; Biomarkers and Imaging of Vulnerable Atherosclerosis in Symptomatic Carotid Artery Disease [BIOVASC], 2014-2018; Barcelona Plaque Study, 2015-2018). Eligible patients had a recent nonsevere (modified Rankin Scale score ≤3) anterior circulation ischemic stroke/TIA and ipsilateral mild carotid stenosis (<50%); ipsilateral moderate carotid stenosis (50%-69%) plus at least 1 of female sex, age <65 years, diabetes mellitus, TIA, or delay >14 days to revascularization; or monocular loss of vision. Patients underwent coregistered carotid 18F-fluorodeoxyglucosePET/CT angiography (≤7 days from inclusion). The primary outcome was 90-day ipsilateral ischemic stroke. Multivariable Cox regression modeling was performed.
Results:
We included 135 patients. All patients started optimal modern-era medical treatment at admission, and 62 (45.9%) underwent carotid revascularization (36 within the first 14 days and 26 beyond). At 90 days, 18 (13.3%) patients had experienced at least 1 stroke recurrence. The risk of recurrence increased progressively according to the SCAIL score (0.0% in patients scoring 0-1, 15.1% scoring 2-3, and 26.7% scoring 4-5; p = 0.04). The adjusted (age, smoking, hypertension, diabetes, carotid revascularization, antiplatelets and statins) hazard ratio for ipsilateral recurrent stroke per 1-point SCAIL increase was 2.16 (95% CI 1.32-3.53; p = 0.002). A score ≥2 had a sensitivity of 100% for recurrence.
Discussion:
The SCAIL score improved the identification of early recurrent stroke in subgroups who did not experience benefit in endarterectomy trials. Randomized trials are needed to test whether a combined stenosis-inflammation strategy will improve selection for carotid revascularization when benefit is currently uncertain.
Classification Of Evidence:
This study provides Class II evidence that, in patients with recent anterior circulation ischemic stroke who do not benefit from carotid revascularization, the SCAIL score accurately distinguishes those at risk for recurrent ipsilateral ischemic stroke.
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