Modern Medical Therapy Versus Carotid Revascularization in Asymptomatic Carotid Stenosis

Background: Landmark trials established carotid endarterectomy (CEA) for asymptomatic carotid stenosis decades ago, but advances in modern medical therapy (MMT) have lowered baseline stroke risk and called the incremental benefit of revascularization into question. We assessed whether CEA or carotid artery stenting (CAS) added to MMT reduces clinically relevant outcomes versus MMT alone. Methods: We systematically searched MEDLINE, Embase, CENTRAL, and SCOPUS from inception to January 5, 2026 (PROSPERO CRD420261292633) for randomized controlled trials (RCTs) comparing MMT alone with MMT plus CEA or CAS in adults with asymptomatic carotid stenosis. Random-effects Mantel-Haenszel odds ratios (ORs) were pooled for the trial-defined primary composite outcome, all stroke, and all-cause mortality. Risk of bias was assessed with RoB 2 and certainty with GRADE. Results: Three RCTs (AMTEC, SPACE-2, CREST-2) enrolling 3,053 patients met criteria; 813 were randomized to CAS, 851 to CEA, and 1,389 to MMT alone. For the primary composite outcome, neither CEA plus MMT (OR 0.50, 95% CI 0.18-1.43; I 2 =56%) nor CAS plus MMT (OR 0.77, 95% CI 0.29-2.06; I 2 =49%) differed significantly from MMT alone. No significant difference was seen for all stroke (CEA: OR 0.77, 95% CI 0.40-1.48; CAS: OR 1.03, 95% CI 0.51-2.11) or all-cause mortality (CEA: OR 0.86, 95% CI 0.58-1.26; CAS: OR 0.77, 95% CI 0.53-1.10). Event rates were uniformly low and certainty of evidence was low to very low, downgraded for imprecision and risk of bias. Findings were robust in fixed-effect and AMTEC-excluded sensitivity analyses. Conclusions: In the contemporary MMT era, randomized evidence does not demonstrate a clear incremental benefit of routine CEA or CAS over MMT alone for stroke or mortality in asymptomatic carotid stenosis, supporting MMT as the foundation of management and a selective, risk-stratified approach to revascularization.