What is the risk of stroke in asymptomatic severe carotid stenosis with and without intervention, using best medical therapy including aspirin (acetylsalicylic acid) and atorvastatin (lipid-lowering medication)?

Stroke Risk in Asymptomatic Severe Carotid Stenosis: Medical Therapy vs. Intervention

For patients with asymptomatic severe carotid stenosis, the annual stroke risk is approximately 1% with best medical therapy alone, compared to approximately 0.5% with intervention plus medical therapy, though this small absolute benefit must be weighed against a 2-3% perioperative stroke/death risk with intervention.

Stroke Risk with Best Medical Therapy Alone

• The annual stroke risk in patients with asymptomatic severe carotid stenosis managed with contemporary best medical therapy has fallen to ≤1% per year 1
• In the Asymptomatic Carotid Surgery Trial (ACST), patients on lipid-lowering therapy had a lower absolute benefit from carotid endarterectomy (0.6% per year) compared to those not on lipid-lowering therapy (1.5% per year) 1
• Modern optimal medical therapy may have further reduced stroke risk compared to older clinical trials, potentially obviating the need for carotid revascularization in many patients 1
• Best medical therapy includes:
  • Daily antiplatelet therapy (typically aspirin) 1, 2, 3
  • Statin therapy (e.g., atorvastatin) 1, 2, 4
  • Blood pressure control 1, 2
  • Diabetes management 1, 2
  • Smoking cessation and lifestyle modifications 1, 2

Stroke Risk with Intervention Plus Medical Therapy

• The aggregate 5-year risk for ipsilateral stroke with carotid endarterectomy (CEA) plus medical therapy was 5.1% compared to 11% for medical therapy alone in the Asymptomatic Carotid Atherosclerosis Study (ACAS), representing a 53% relative risk reduction 1
• This translates to an approximate annual stroke risk of 1% with CEA plus medical therapy versus 2.2% with medical therapy alone in older studies 1
• However, with modern medical therapy, the benefit of intervention has likely decreased 1
• The perioperative risk of stroke or death with CEA is approximately 1.5-3% in asymptomatic patients 1
• For carotid artery stenting (CAS), the perioperative risk is higher at approximately 2.2-4% 1, 5

Key Considerations for Clinical Decision-Making

• The American Heart Association recommends that CEA may be reasonable in asymptomatic patients with >70% stenosis if the perioperative risk is low (<3%), but acknowledges that its effectiveness compared to contemporary medical management is not well established 1, 2
• The European Society of Cardiology recommends against routine revascularization in asymptomatic patients with carotid stenosis who have a life expectancy <5 years 3
• Patient selection for intervention should consider:
  • Age (benefits of CEA were confined to patients <75 years in ACST) 1
  • Comorbidities and life expectancy 2, 3
  • Surgical risk factors 1, 2
  • Presence of high-risk plaque features (e.g., intraplaque hemorrhage, microemboli on transcranial Doppler) 5

Post-Management Follow-up

• Annual duplex ultrasound is recommended to assess disease progression or regression and response to treatment 1, 2
• Patients who have progression of stenosis by ≥2 categories in 1 year are at higher risk of ipsilateral ischemic events 1
• For patients who undergo intervention:
  • After CEA, aspirin or clopidogrel should be continued for 1-3 months, then transitioned to single antiplatelet therapy indefinitely 6
  • After CAS, dual antiplatelet therapy with aspirin and clopidogrel is recommended for at least 1 month 6

Common Pitfalls and Caveats

• Not recognizing that what is often accepted as "best medical therapy" is usually suboptimal; truly intensive medical therapy includes lifestyle modification, particularly smoking cessation and dietary changes 5
• Failing to identify patients who might benefit most from intervention (approximately 15% of asymptomatic patients) based on high-risk features 5
• Subjecting patients to intervention without evidence of high-risk features, when their stroke risk with modern medical therapy alone may be very low 5
• Not considering that most elderly patients would be better treated with CEA than CAS if intervention is necessary 5
• Overlooking that the combination of dietary modification, physical exercise, and use of aspirin, a statin, and an antihypertensive agent can provide a cumulative relative stroke risk reduction of up to 80% 7