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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)

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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(24)00085-3

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)

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

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

Content summarized and formatted by NeuroTrials.ai.

ECST-2

(2025)

Objective

To determine whether patients with asymptomatic or low-to-intermediate risk symptomatic carotid stenosis benefit from revascularisation in addition to optimised medical therapy (OMT).

Study Summary

• In patients with ≥50% carotid stenosis and <20% 5-year stroke risk (based on CAR score), adding revascularisation to OMT did not improve outcomes at 2 years compared to OMT alone.

Intervention

OMT alone versus OMT plus carotid revascularisation (CEA or CAS).

Inclusion Criteria

Adults ≥18 years with carotid stenosis ≥50% (NASCET criteria), with either asymptomatic status or symptomatic status and <20% 5-year stroke risk (CAR score).

Study Design

Arms: OMT alone (n=214) vs OMT + Revascularisation (n=214)

Patients per Arm: OMT: 214, Revascularisation: 214

Outcome

• Win ratio for primary hierarchical outcome (death, stroke, MI, silent infarction): 1.01 (95% CI 0.60–1.70), p=0.97. <br>• No significant difference in nonfatal stroke, MI, or silent infarcts. <br>• Ipsilateral stroke: 2.9% in OMT vs 6.2% in revascularisation (p=0.052). <br>• Silent infarcts: 9.4% (OMT) vs 7.8% (revascularisation). <br>• No difference in functional outcomes or all-cause mortality.

Bottom Line

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

Study Design

Study Type: Multicenter, open-label, randomized controlled trial with blinded outcome adjudication
Randomization: Yes
Blinding: Outcome adjudicators and imaging assessors were blinded
Sample Size: 429
Follow-up: 2 years (interim analysis)
Centers: 30
Countries: UK, Netherlands, Switzerland, Canada, Italy

Primary Outcome

Definition: Hierarchical composite: periprocedural death, fatal stroke/MI, non-fatal stroke, non-fatal MI, silent cerebral infarction

Control	Intervention	HR/OR	P-value
11.4% wins	11.3% wins	- (0.60–1.70)	0.97

Limitations & 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

Citation

Lancet Neurol. 2025;24:389–399

View Original Publication →

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)

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Baseline Characteristics

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

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