Modern Management of Asymptomatic Carotid Stenosis: A Meta-Analysis of CREST-2, SPACE-2, and ECST-2

Recent randomized trials (CREST-2, SPACE-2, and ECST-2) have compared carotid revascularization (carotid endarterectomy [CEA] or carotid artery stenting [CAS]) plus contemporary medical therapy (CMT) versus CMT alone in asymptomatic carotid stenosis. ECST-2 included both asymptomatic and low-risk symptomatic patients, introducing clinical heterogeneity. Individual trials reported low event rates and limited statistical power.

To evaluate whether carotid revascularization reduces long-term ipsilateral stroke (> 30 days) compared with CMT alone and to assess periprocedural complications.

Phase 3/4 randomized controlled trials published after 2020 were included. The primary outcome was long-term ipsilateral stroke excluding periprocedural events. Periprocedural complications (30-day stroke, myocardial infarction, or death) were analyzed separately. Random-effects models were used. Subgroup analyses by modality (CEA vs. CAS) included CREST-2 and SPACE-2. Sensitivity analyses excluding ECST-2 and using split-control methodology for SPACE-2 were performed.

Three trials (5 arms; 3438 patients) were included. Median follow-up was 4.0 years in CREST-2, 5.0 years in SPACE-2, and 2.0 years in ECST-2. In the primary pooled analysis including ECST-2, revascularization showed a nonsignificant reduction in long-term ipsilateral stroke (RR 0.51; 95% CI 0.21-1.29; p = 0.16; I² = 70%) and a borderline increase in periprocedural complications (RR 2.78; p = 0.06). Sensitivity analyses excluding ECST-2 suggested reduced long-term ipsilateral stroke with revascularization (RR 0.35; 95% CI 0.21-0.58; p < 0.0001; I² = 0%; ARR 2.74%; NNT = 37) but increased periprocedural complications (RR 4.54; p = 0.004; I² = 0%; ARI 1.45%; NNH = 69). Subgroup analyses suggested a possible benefit with CAS, whereas CEA showed a nonsignificant trend; however, subgroup analyses were underpowered. Split-control sensitivity analyses for SPACE-2 yielded directionally similar findings with wider confidence intervals.

The primary pooled analysis was inconclusive and demonstrated substantial heterogeneity. Sensitivity analyses restricted to purely asymptomatic populations suggested that carotid revascularization may reduce long-term ipsilateral stroke but increase periprocedural complications. Contemporary medical therapy remains the foundation of management for asymptomatic carotid stenosis, while revascularization should be reserved for carefully selected patients after individualized risk assessment and shared decision-making.