An umbrella review and second-order meta-analysis of CAS versus CEA for carotid stenosis.

Background: Carotid artery stenting (CAS) and carotid endarterectomy (CEA) are the two principal revascularization strategies for carotid stenosis, but their comparative safety and efficacy remain debated, particularly across different symptom statuses and follow-up periods. Objective: To conduct an updated umbrella meta-analysis (UMA) of published meta-analyses (MAs) comparing the efficacy and safety of CAS versus CEA in patients with carotid stenosis, and to examine whether treatment effects differed according to symptom status and timing of outcome assessment. Methods: A systematic literature search was performed in PubMed, Embase, Web of Science, and the Cochrane Library from January 2014 to July 2026. Meta-analyses comparing CAS with CEA based on randomized controlled trials or cohort studies were included. Methodological quality was assessed using AMSTAR 2. Random-effects models were applied for second-order pooled analyses. Prespecified subgroup analyses were conducted according to symptom status and temporal stratification, including 30-day postoperative and long-term follow-up periods. Primary-study overlap was quantified separately for each outcome using citation matrices and the corrected covered area (CCA). Leave-one-out and Results: Twenty-one MAs were included. In the overall pooled analyses, CAS was associated with higher risks of death (OR: 1.13, 95% CI: 1.07 ~ 1.19), stroke (OR: 1.53, 95% CI: 1.41 ~ 1.65), and restenosis (OR: 1.56, 95% CI: 1.19 ~ 2.04), but lower risks of myocardial infarction (MI) (OR: 0.52, 95% CI: 0.46 ~ 0.59) and cranial nerve palsy (CNP) (OR: 0.06, 95% CI: 0.03 ~ 0.11) compared with CEA. No significant differences were observed for ipsilateral stroke or disabling stroke. The excess risks of death and stroke with CAS were numerically greater during the 30-day postoperative period than during long-term follow-up. Outcome-specific CCA values ranged from 12 to 38%, indicating high-to-very-high primary-study overlap. Conclusions remained unchanged in leave-one-out and overlap-reduced sensitivity analyses. Conclusion: Among patients undergoing carotid revascularization, CEA was associated with lower pooled risks of stroke and restenosis, whereas CAS was associated with lower risks of MI and cranial nerve palsy. The small mortality difference should be interpreted cautiously because of heterogeneity in follow-up, symptom status, outcome definitions, and substantial primary-study overlap. The higher stroke risk associated with CAS appeared to be driven mainly by non-disabling events. These findings support individualized procedural selection after an indication for revascularization has been established. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42024627431, Identifier CRD42024627431.