In a patient with a significant carotid atherosclerotic plaque, is dual antiplatelet therapy indicated or is single‑agent aspirin or clopidogrel sufficient?

Dual Antiplatelet Therapy in Significant Carotid Plaque

For patients with asymptomatic significant carotid stenosis (≥50%), single antiplatelet therapy with aspirin 75-100 mg daily or clopidogrel 75 mg daily is recommended; dual antiplatelet therapy is not indicated and increases bleeding risk without proven benefit. 1

Clinical Decision Algorithm

Step 1: Determine Symptom Status

Asymptomatic carotid stenosis (≥50%):

• Use single antiplatelet therapy only 1
• First-line: aspirin 75-100 mg daily 1
• Alternative: clopidogrel 75 mg daily (preferred if diabetes, aspirin intolerance, or peripheral arterial disease) 1
• Do NOT use dual antiplatelet therapy – no benefit demonstrated and bleeding risk outweighs any theoretical advantage 1, 2

Symptomatic carotid stenosis (recent stroke/TIA within 21 days):

• If minor stroke (NIHSS ≤3) or high-risk TIA (ABCD² ≥4) presenting within 24 hours:
  • Loading: clopidogrel 300-600 mg + aspirin 160-325 mg 1
  • Maintenance: clopidogrel 75 mg + aspirin 75-100 mg daily for exactly 21 days 1
  • Then switch to single agent indefinitely 1
• If moderate-to-severe stroke (NIHSS >3) or presentation >24 hours:
  • Use single antiplatelet therapy only 1

Step 2: Peri-Procedural Management

For carotid endarterectomy (CEA):

• Continue single antiplatelet therapy peri-operatively 1
• Some surgeons prefer DAPT peri-procedurally, reducing to single agent from day 1 post-CEA 1
• Maintain single agent for 1-3 months post-procedure 1

For carotid artery stenting (CAS):

• Load clopidogrel prior to stenting 1
• Continue DAPT for 1-3 months post-stenting (4-6 weeks for single-layer stents, up to 3 months for mesh stents) 1
• Then transition to single antiplatelet therapy 1

Step 3: Consider Dual Pathway Strategy (Aspirin + Rivaroxaban)

For very high-risk patients with asymptomatic ≥50% stenosis or history of carotid revascularization:

• Consider aspirin 100 mg + rivaroxaban 2.5 mg twice daily 1
• Based on COMPASS trial subgroup (1,919 carotid patients) 1
• Important caveat: Benefit in carotid subgroup did not reach statistical significance 1
• Increases bleeding risk; reserve for patients with low bleeding risk and very high ischemic risk 1

Evidence Quality and Nuances

Why DAPT is NOT recommended for stable asymptomatic carotid stenosis:

• The only randomized trial (Asymptomatic Cervical Bruit Study) with 188 patients per arm failed to show superiority of aspirin versus placebo 1
• Observational studies show SAPT reduces MACE, but DAPT (aspirin + clopidogrel) has no benefit over SAPT in asymptomatic patients 1, 2
• Modern medical therapy has dramatically reduced stroke rates in asymptomatic patients, making the risk-benefit ratio of DAPT unfavorable 1

Recent evidence supporting ticagrelor monotherapy:

• In the THALES trial subgroup analysis, ticagrelor monotherapy was superior to aspirin monotherapy in preventing stroke, MI, or death at 90 days in patients with ipsilateral atherosclerotic carotid stenosis (HR 0.68,95% CI 0.53-0.88, P=0.003) 1
• No significant difference in bleeding events between ticagrelor and aspirin groups 1
• This applies to recently symptomatic patients, not asymptomatic stenosis 1

Common Pitfalls to Avoid

• Do not extrapolate acute stroke DAPT protocols to chronic asymptomatic carotid stenosis – the 21-day DAPT regimen is only for minor stroke/high-risk TIA within 24 hours of onset 1
• Do not continue DAPT beyond 1-3 months post-revascularization – bleeding risk outweighs benefit after this period 1
• Do not use DAPT as a substitute for intensive medical therapy (statins targeting LDL-C <55 mg/dL, blood pressure control, lifestyle modification) – these interventions provide greater stroke risk reduction 1
• Do not forget that antiplatelet therapy does not abolish stroke risk – modern medical therapy reduces but does not eliminate risk, and revascularization may still be needed in selected high-risk patients 1

Comprehensive Medical Management Beyond Antiplatelets

All patients with significant carotid stenosis require:

• Intensive statin therapy (LDL-C target <55 mg/dL) with ezetimibe or PCSK9 inhibitor if needed 1
• Blood pressure control (ACE inhibitors like ramipril provide additional vasculoprotective effects beyond BP reduction) 1
• Diabetes optimization 1
• Smoking cessation 1
• Dietary modification and physical exercise 1