Dual Antiplatelet Therapy vs Anticoagulation After Small Stroke
For patients with minor ischemic stroke (NIHSS 0-3) or high-risk TIA of noncardioembolic origin, initiate dual antiplatelet therapy (aspirin + clopidogrel) within 24 hours and continue for exactly 21 days, then transition to single antiplatelet therapy; reserve anticoagulation exclusively for cardioembolic stroke, particularly atrial fibrillation. 1
Decision Algorithm: DAPT vs Anticoagulation
Step 1: Determine Stroke Mechanism
- Cardioembolic stroke (especially atrial fibrillation): Use anticoagulation (apixaban, rivaroxaban, dabigatran, or warfarin), NOT antiplatelet therapy 2
- Noncardioembolic stroke: Proceed to Step 2 for antiplatelet selection 1
Step 2: Assess Stroke Severity and Timing
- Minor stroke (NIHSS ≤3) or high-risk TIA (ABCD2 ≥4) presenting within 24 hours: Use dual antiplatelet therapy 1
- Moderate-to-severe stroke (NIHSS >3): Use single antiplatelet therapy only 1
- Presentation >24 hours after symptom onset: Use single antiplatelet therapy only 1
Step 3: DAPT Protocol for Eligible Patients
- Loading doses: Clopidogrel 300-600 mg + aspirin 160-325 mg within 24 hours of symptom onset (ideally within 12 hours) 1, 2
- Maintenance: Clopidogrel 75 mg daily + aspirin 75-100 mg daily for exactly 21 days 1, 3
- After 21 days: Transition to single antiplatelet therapy (aspirin 75-100 mg daily OR clopidogrel 75 mg daily) indefinitely 1, 2
Evidence Supporting 21-Day Duration
The pooled analysis of CHANCE and POINT trials (10,051 patients) demonstrated that DAPT reduces major ischemic events by 34% compared to aspirin alone (6.5% vs 9.1%, HR 0.70), but this benefit is confined entirely to the first 21 days (HR 0.66 for days 0-21 vs no benefit days 22-90). 3 Beyond 21 days, the bleeding risk (HR 1.88-2.42 for major hemorrhage) negates any ischemic benefit. 3, 4
Critical Exclusions and Contraindications
Do NOT use DAPT if:
- Intracranial hemorrhage not yet ruled out on neuroimaging 1, 2
- Patient received IV alteplase within past 24 hours (delay antiplatelet initiation until post-thrombolysis scan excludes hemorrhage) 1
- High bleeding risk conditions present 4
- Urgent carotid endarterectomy planned (consider aspirin monotherapy instead to reduce perioperative bleeding) 1
Do NOT use antiplatelet therapy as substitute for thrombolysis or thrombectomy in eligible patients 1
Anticoagulation Indications After Stroke
Anticoagulation is indicated specifically for:
- Atrial fibrillation with CHA2DS2-VASc ≥2 (males) or ≥3 (females): Use DOAC (apixaban, rivaroxaban, dabigatran) or warfarin 2
- Mechanical prosthetic heart valves: Use warfarin (INR 2.5-3.5), NOT DOACs 2
- Other cardioembolic sources: Left ventricular thrombus, recent MI with LV dysfunction 2
The usefulness of anticoagulation for severe carotid stenosis or nonocclusive intraluminal thrombus remains uncertain and is not well established. 1
Common Pitfalls to Avoid
- Do NOT continue DAPT beyond 21-30 days - this significantly increases hemorrhage risk (NNH 113-258) without additional stroke prevention benefit 3, 4
- Do NOT delay DAPT initiation beyond 24 hours - efficacy is time-dependent with maximum benefit when started within 12 hours 1, 2
- Do NOT use ticagrelor instead of clopidogrel - ticagrelor is not recommended over aspirin in acute minor stroke treatment 1
- Do NOT use glycoprotein IIb/IIIa inhibitors (abciximab) - these are potentially harmful in acute ischemic stroke 1, 2
Special Populations
- Dysphagia: Administer aspirin 81 mg + clopidogrel 75 mg via enteral tube, or aspirin 325 mg rectal suppository daily 1, 2
- Age ≥70 years: No dose adjustment needed; COMMIT trial showed no excess bleeding risk with DAPT in elderly patients 2
- Patients already on antiplatelet therapy: DAPT still reduces ischemic stroke risk regardless of premorbid antiplatelet use (HR 0.69 vs 0.75, p=0.685) 5