← Back

ECST-2

Carotid Artery Stenting or Endarterectomy Versus Best Medical Therapy Alone in Patients With Symptomatic or Asymptomatic Carotid Stenosis at Low to Intermediate Risk of Stroke (ECST-2)

Share Share Copied! Compare

Year of Publication: 2025

Authors: Simone J A Donners, Twan J van Velzen, Suk Fun Cheng, ..., on behalf of the ECST-2 investigators

Journal: The Lancet Neurology

Citation: Lancet Neurol. 2025;24:389–399

Link: https://doi.org/10.1016/S1474-4422(25)00107-3

PDF: https://www.thelancet.com/action/showPdf...%2825%2900107-3

Clinical Question

Does revascularization reduce stroke risk when added to optimized medical therapy in patients with asymptomatic or low-to-intermediate risk symptomatic carotid stenosis?

Bottom Line

Among patients with low-to-intermediate risk carotid stenosis, adding carotid revascularization to optimized medical therapy did not reduce stroke, MI, or death over 2 years compared with medical therapy alone.

        Major Points
        Multicenter RCT with 429 patients with ≥50% carotid stenosis and low/intermediate stroke risk
Randomized to optimized medical therapy (OMT) alone or OMT plus revascularization (CEA or CAS)
Primary outcome: no difference using win ratio method (1.01, 95% CI 0.60–1.70, p=0.97)
Stroke rates were low in both groups: 2-year ipsilateral stroke 2.9% (OMT) vs. 6.2% (revasc.)
Majority of infarcts on imaging were silent (90%); no difference in silent infarcts
Findings support individualized risk-based approach; revascularization may not benefit low-risk patients

      

Design

Study Type: Multicenter, open-label, randomized controlled trial with blinded outcome adjudication

Randomization: 1

Blinding: Outcome adjudicators and imaging assessors were blinded

Enrollment Period: March 1, 2012 – Oct 31, 2019

Follow-up Duration: 2 years (interim analysis)

Centers: 30

Countries: UK, Netherlands, Switzerland, Canada, Italy

Sample Size: 429

Analysis: Intention-to-treat; primary outcome analyzed with win ratio method (Finkelstein–Schoenfeld); secondary outcomes via Kaplan–Meier estimates and Cox models

Inclusion Criteria

Age ≥18 years
Carotid stenosis ≥50% (NASCET criteria)
Symptomatic with 5-year stroke risk <20% by CAR score OR asymptomatic ≥180 days
Eligible for revascularization and OMT

Exclusion Criteria

Prior CEA or CAS on index artery
Contraindication to MRI or study procedures
Predicted 5-year stroke risk ≥20%

Baseline Characteristics

Age, years: 72 (IQR 65–78)

Sex - Female: 31%

Sex - Male: 69%

Symptomatic: 40%

Asymptomatic: 60%

BMI: 27.4 (OMT) vs 27.7 (Revasc)

Hypertension: 76% (OMT), 77% (Revasc)

Diabetes: 30% (OMT), 25% (Revasc)

Smoking - Current: 22% (OMT), 18% (Revasc)

Statin use: 97% (OMT), 96% (Revasc)

Antiplatelet use: 93% (OMT), 89% (Revasc)

Arms

Field	OMT plus Revascularization	Control
Intervention	Optimized medical therapy plus carotid endarterectomy (CEA) or stenting (CAS)	Optimized medical therapy including antiplatelets, statins, BP and lifestyle management
Duration	Up to 2 years follow-up	Up to 2 years follow-up

Outcomes

Outcome	Type	Control	Intervention	HR / OR / RR	P-value
Hierarchical composite: periprocedural death, fatal stroke/MI, non-fatal stroke, non-fatal MI, silent cerebral infarction	Primary	11.4% wins	11.3% wins	0.10%	0.97
Ipsilateral stroke	Secondary	2.9%	6.2%	0.45	0.052
Any stroke	Secondary	5.9%	8.6%	0.64	0.14
Myocardial infarction	Secondary	4.9%	2.5%	2.00	0.10
Silent cerebral infarction	Secondary	9.4%	7.8%		0.82
Stroke	Adverse	5.9%	8.6%		0.14
Myocardial Infarction	Adverse	4.9%	2.5%		0.10
Death	Adverse	6.4%	6.3%		0.47

Subgroup Analysis

No significant heterogeneity across prespecified subgroups (age, sex, stenosis severity, symptom status); all favored OMT alone or were neutral

Criticisms

Interim analysis with limited 2-year follow-up; full 5-year results pending
Power limited due to low event rates and COVID-19-related imaging follow-up loss
CAR score, though predictive, has not been externally validated
Majority underwent CEA, not CAS, limiting generalizability to stenting

Funding

NIHR, Stroke Association, Swiss National Science Foundation, ZonMw (Netherlands), Leeds Neurology Foundation

Based on: ECST-2 (The Lancet Neurology, 2025)