What is the recommended treatment for asymptomatic carotid stenosis, considering the Crest 2 trial?

Treatment of Asymptomatic Carotid Stenosis: CREST-2 Findings

Based on the landmark CREST-2 trial published in 2025, carotid artery stenting plus intensive medical management significantly reduces the risk of stroke or death compared to intensive medical management alone in patients with high-grade (≥70%) asymptomatic carotid stenosis, while carotid endarterectomy did not demonstrate significant benefit over medical therapy alone. 1

CREST-2 Trial Results: The Definitive Evidence

The CREST-2 trial fundamentally changes our approach to asymptomatic carotid stenosis by providing the first modern comparison of revascularization versus contemporary optimal medical therapy:

Stenting Trial Outcomes

• 4-year primary outcome incidence: 2.8% with stenting versus 6.0% with medical therapy alone (P = 0.02) 1
• This represents an absolute risk reduction of 3.2% favoring stenting 1
• Critical caveat: From day 0-44, the stenting group experienced 7 strokes and 1 death versus zero events in the medical therapy group, highlighting significant periprocedural risk 1

Endarterectomy Trial Outcomes

• 4-year primary outcome incidence: 3.7% with endarterectomy versus 5.3% with medical therapy alone (P = 0.24, not significant) 1
• From day 0-44, the endarterectomy group had 9 strokes versus 3 strokes in the medical therapy group 1
• The lack of statistical significance means endarterectomy cannot be recommended over medical therapy alone based on this highest-quality, most recent evidence 1

Recommended Treatment Algorithm

Step 1: Confirm Stenosis Severity and Symptom Status

• Use duplex ultrasound with peak systolic velocity (PSV) thresholds: ≥230 cm/s indicates ≥70% stenosis 2
• Verify the patient is truly asymptomatic (no TIA, stroke, or amaurosis fugax in the ipsilateral territory within the past 6 months) 2

Step 2: Initiate Intensive Medical Management (ALL Patients)

This is mandatory regardless of whether revascularization is pursued:

• Antiplatelet therapy: Low-dose aspirin (75-100 mg daily) should be considered if bleeding risk is low (Class IIa, Level C) 2
• Statin therapy: High-intensity statin targeting LDL-C <55 mg/dL 2
• Blood pressure control: Target <140/90 mmHg (or <130/80 mmHg if tolerated) 2
• Smoking cessation: Mandatory, as the 60-70% decline in stroke rates in medically treated patients from 1995-2010 was partly attributed to lower smoking incidence 2
• Diabetes management: Optimize glycemic control 2

Step 3: Risk Stratification for Revascularization Consideration

High-risk features that increase stroke risk on medical therapy alone include: 2

• Contralateral TIA or stroke
• Ipsilateral silent infarction on brain imaging
• Stenosis progression >20%
• Spontaneous embolization on transcranial Doppler
• Impaired cerebrovascular reserve
• Echolucent plaques or intraplaque hemorrhage on imaging

Step 4: Revascularization Decision

For patients with ≥70% stenosis:

Option A: Carotid Artery Stenting + Intensive Medical Management

• This is the only revascularization approach with proven benefit over medical therapy alone in the modern era 1
• Consider this option when:
  • Patient has high-risk plaque features 2
  • Life expectancy >4 years to realize the benefit 1
  • Patient accepts the 0.6% periprocedural stroke/death risk (8 events in 1245 patients within 44 days) 1

Option B: Intensive Medical Management Alone

• This is a reasonable default strategy given:
  • The 60-70% decline in stroke rates with modern medical therapy 2
  • SPACE-2 trial showed 0.9% 1-year event rate with optimal medical therapy alone versus 2.5% with CEA and 3.0% with CAS 2
  • No periprocedural risk 1

Option C: Carotid Endarterectomy + Intensive Medical Management

• Cannot be recommended based on CREST-2 results showing no significant benefit (P = 0.24) 1
• Historical trials (ACAS, ACST-1) showed benefit, but these enrolled patients from 1987-2003 who did not receive modern medical therapy 2
• The absolute risk reduction was only 4.6% at 10 years in ACST-1, meaning 95% of patients underwent unnecessary surgery 2

Critical Pitfalls to Avoid

Pitfall 1: Applying Outdated Evidence

• Do not rely on ACAS (1995) or ACST-1 (2004) to justify routine endarterectomy 2
• These trials predated modern statin therapy, intensive blood pressure control, and smoking cessation programs 2
• The medical therapy arms in these trials had 11.0% and 11.8% 5-year stroke rates respectively—far higher than the 5.3% seen in CREST-2's medical therapy arm 2, 1

Pitfall 2: Ignoring Periprocedural Risk

• Both stenting and endarterectomy carry significant early hazard 1
• The benefit of revascularization accrues over years, not months 1
• Patients with limited life expectancy (<4 years) are unlikely to benefit 1

Pitfall 3: Gender Considerations

• Historical data suggested women benefit less from CEA at 5 years, though benefit emerged at 10 years (ARR 5.8%) 2
• CREST-2 did not report gender-specific outcomes, so apply the overall trial results 1

Pitfall 4: Age Misconceptions

• Age >75 years was NOT associated with ipsilateral stroke reduction at 5-10 years in ACST-1 2
• Do not withhold medical therapy based on age, but be cautious about revascularization in elderly patients given periprocedural risks 2

Monitoring Strategy

For patients managed medically (with or without revascularization):

• Annual duplex ultrasound to assess stenosis progression 2
• Patients with stenosis progression ≥2 categories in 1 year are at high risk and should be reconsidered for intervention 2
• Assess adherence to antiplatelet therapy, statin therapy, and cardiovascular risk factor control 2

The Bottom Line

The CREST-2 trial represents a paradigm shift: for asymptomatic carotid stenosis ≥70%, carotid artery stenting plus intensive medical management is superior to intensive medical management alone, while carotid endarterectomy showed no significant benefit. 1 However, the absolute benefit of stenting is modest (3.2% absolute risk reduction over 4 years), and the periprocedural risk is real. Intensive medical management alone remains a highly effective and safe strategy for most patients, particularly given the dramatic improvements in stroke prevention with modern pharmacotherapy. 2, 1