In a patient with a recent (within 24 hours) mild non‑cardioembolic ischemic stroke (NIHSS ≤5) or high‑risk transient ischemic attack, should I add ticagrelor to aspirin?

Ticagrelor in Acute Minor Stroke or High-Risk TIA: Not Recommended

Do not add ticagrelor to aspirin for patients with recent mild non-cardioembolic ischemic stroke (NIHSS ≤5) or high-risk TIA; instead, use the proven aspirin plus clopidogrel regimen for exactly 21 days. 1, 2

Why Clopidogrel, Not Ticagrelor

The evidence strongly favors aspirin plus clopidogrel over aspirin plus ticagrelor in this population:

• The European Stroke Organisation gives a strong recommendation (high-quality evidence) for 21 days of aspirin plus clopidogrel in patients with non-cardioembolic minor ischemic stroke or high-risk TIA presenting within 24 hours. 2

• In contrast, the ESO gives only a weak recommendation (moderate-quality evidence) for 30 days of aspirin plus ticagrelor in the same population. 2

• The THALES trial (2020) showed that ticagrelor plus aspirin reduced stroke or death from 6.6% to 5.5% (HR 0.83) over 30 days, but severe bleeding increased five-fold (0.5% vs 0.1%, P=0.001). 3

• Earlier guidelines explicitly caution that "ticagrelor increases the risk of fatal intracranial hemorrhage compared with clopidogrel and should be avoided in those with a prior history of ICH," and recommend weighing the increased intracranial bleeding risk when considering ticagrelor in patients with prior stroke or TIA. 4

The Proven Regimen: Aspirin Plus Clopidogrel

Loading doses (within 24 hours of symptom onset):

• Clopidogrel 300 mg (acceptable range 300–600 mg). 1
• Aspirin 160–325 mg. 1

Maintenance phase (days 2–21):

• Clopidogrel 75 mg once daily. 1
• Aspirin 75–100 mg once daily. 1

After day 21:

• Switch to single antiplatelet therapy (aspirin 75–100 mg daily OR clopidogrel 75 mg daily) indefinitely. 1

Eligibility Criteria

You should use dual antiplatelet therapy only when ALL of the following are met:

• Minor ischemic stroke (NIHSS ≤3) or high-risk TIA (ABCD² ≥4). 1
• Non-cardioembolic mechanism (no atrial fibrillation). 1
• Presentation within 24 hours of symptom onset (benefit extends to 72 hours but diminishes). 1
• Intracranial hemorrhage excluded on neuroimaging. 1
• No IV alteplase in the preceding 24 hours. 1

Why the 21-Day Duration Matters

• The benefit of dual antiplatelet therapy is confined to the first 21 days; beyond this window, bleeding risk outweighs any stroke-prevention benefit (HR for major bleeding 2.22–2.32 after 90 days). 1

• The THALES trial used a 30-day regimen, but pooled analysis shows most ischemic events occur in the first week, making the 21-day clopidogrel-based regimen more favorable from a risk-benefit standpoint. 1, 3

Critical Contraindications

Do NOT use dual antiplatelet therapy (with either clopidogrel or ticagrelor) when:

• NIHSS >3 (moderate-to-severe stroke)—use aspirin monotherapy instead. 1
• Presentation >72 hours after symptom onset. 1
• Active bleeding, severe thrombocytopenia, or high bleeding risk. 1
• Prior intracranial hemorrhage (especially relevant for ticagrelor). 4

Common Pitfalls to Avoid

• Never extend dual antiplatelet therapy beyond 21–30 days unless a separate cardiac indication (e.g., recent coronary stent) exists; prolonged use markedly increases bleeding without additional stroke prevention. 1

• Never substitute ticagrelor for clopidogrel based solely on its use in acute coronary syndromes; the stroke population has different bleeding risks and the evidence base is weaker. 4, 2

• Never delay initiation beyond 24 hours when eligibility criteria are met; maximal efficacy occurs when started within the first 12–24 hours. 1