For a recent minor non‑cardioembolic ischemic stroke (NIHSS ≤ 3) or high‑risk transient ischemic attack without contraindications, how many days should dual antiplatelet therapy with aspirin and clopidogrel be given?

Duration of Dual Antiplatelet Therapy After Minor Stroke or High-Risk TIA

For patients with minor non-cardioembolic ischemic stroke (NIHSS ≤ 3) or high-risk TIA (ABCD² ≥ 4), dual antiplatelet therapy with aspirin and clopidogrel should be continued for exactly 21 days, then switched to single antiplatelet therapy indefinitely. 1, 2

Treatment Protocol

Loading Dose (Day 1)

• Clopidogrel 300–600 mg plus aspirin 160–325 mg administered within 24 hours of symptom onset (ideally within 12 hours). 1, 2
• The 300 mg clopidogrel dose used in the CHANCE trial may carry modestly lower bleeding risk than the 600 mg dose used in POINT. 1

Maintenance Phase (Days 2–21)

• Clopidogrel 75 mg daily plus aspirin 75–100 mg daily for exactly 21 days. 1, 2
• The benefit of dual therapy is confined to the first 21 days, with most stroke prevention occurring in the first week. 1, 2

Transition to Long-Term Therapy (After Day 21)

• Switch to single antiplatelet therapy with either:
  • Aspirin 75–100 mg daily (first-line), or 1, 2
  • Clopidogrel 75 mg daily (alternative for aspirin intolerance). 1, 2

Evidence Supporting 21-Day Duration

The pooled analysis of CHANCE and POINT trials (10,051 patients) demonstrates that dual antiplatelet therapy reduces major ischemic events within the first 21 days (hazard ratio 0.66,95% CI 0.56–0.77), but provides no additional benefit from day 22 to day 90. 3

• Within 21 days: 5.2% event rate with dual therapy vs. 7.8% with aspirin alone (32% relative risk reduction). 3
• From day 22–90: No significant difference in event rates between groups. 3
• Major hemorrhage risk increases with dual therapy (relative risk 1.88–1.90) but remains low in absolute terms. 2, 3

Critical Timing Considerations

• Initiate within 12–24 hours of symptom onset for maximal benefit; efficacy persists if started up to 72 hours. 1, 2
• Beyond 72 hours: Dual therapy is not recommended; use single antiplatelet therapy instead. 1
• If IV alteplase was given: Wait at least 24 hours post-thrombolysis before starting antiplatelet therapy. 1

Why Not Longer Than 21 Days?

Extending dual antiplatelet therapy beyond 21–30 days significantly increases major hemorrhage risk (hazard ratio 2.22–2.32) without additional stroke-prevention benefit. 1, 2

• The POINT trial showed that treating 1,000 patients for 90 days prevents 15 ischemic strokes but causes 5 major hemorrhages. 1
• Bleeding risk outweighs benefit after the acute high-risk period. 2, 4

Common Pitfalls to Avoid

• Never continue dual therapy beyond 30 days unless a separate cardiac indication (e.g., recent coronary stent) exists. 1, 2
• Never delay initiation beyond 24 hours when eligibility criteria are met; time-dependent efficacy is critical. 1, 2
• Never use dual therapy as a substitute for thrombolysis or thrombectomy in eligible patients. 1, 2
• Never use dual therapy in moderate-to-severe stroke (NIHSS > 3) or low-risk TIA (ABCD² < 4). 1, 5

Guideline Endorsement

The European Stroke Organisation issued a strong recommendation (Class I, Level A evidence) for 21 days of aspirin-clopidogrel dual therapy based on high-quality randomized trial data from CHANCE and POINT. 6