Antiplatelet Management in Ischemic Stroke
Acute Phase: Minor Stroke and High-Risk TIA
For patients with minor ischemic stroke (NIHSS ≤3) or high-risk TIA (ABCD2 ≥4), dual antiplatelet therapy (DAPT) with aspirin and clopidogrel should be initiated as early as possible—ideally within 12-24 hours of symptom onset—after excluding intracranial hemorrhage on neuroimaging. 1
Loading Dose Regimen
- Aspirin: 160-325 mg loading dose 1
- Clopidogrel: 300 mg (CHANCE trial) or 600 mg (POINT trial) loading dose 1
Maintenance Regimen
- Aspirin: 81 mg daily 1
- Clopidogrel: 75 mg daily 1
- Duration: Continue DAPT for 21 days, then transition to single antiplatelet therapy 1
Recent evidence supports extending the initiation window: Patients who present between 24-72 hours after symptom onset still benefit from DAPT with similar efficacy and safety profiles, though the benefit appears strongest when initiated earliest. 2
Alternative DAPT Regimen for Mild-Moderate Stroke
For patients with NIHSS ≤5 or high-risk TIA, an alternative regimen exists:
- Loading: Aspirin 300-325 mg + ticagrelor 180 mg 1
- Maintenance: Aspirin 75-100 mg daily + ticagrelor 90 mg twice daily 1
- Duration: 30 days, followed by single antiplatelet therapy 1
However, ticagrelor is not recommended over aspirin in acute treatment of minor stroke based on current evidence. 1
Acute Phase: Moderate-to-Severe Stroke
For patients with moderate-to-severe ischemic stroke (NIHSS >5) who are not candidates for thrombolysis or thrombectomy, aspirin monotherapy should be initiated within 24-48 hours of symptom onset. 1
- Dose: 160-325 mg loading dose, then 81-325 mg daily 1
- Route: Oral preferred; rectal (325 mg) or nasogastric tube (81 mg or clopidogrel 75 mg) if swallowing impaired 1
Critical Timing Considerations
Aspirin should NOT be given within 24 hours of IV thrombolysis (alteplase). 1 While aspirin may be considered in patients with concomitant conditions where withholding poses substantial risk, it is generally delayed 24 hours post-thrombolysis. 1
Aspirin is not a substitute for acute interventions: It should never replace IV thrombolysis or mechanical thrombectomy in eligible patients. 1
Long-Term Secondary Prevention
After completing the short-term DAPT course (21-30 days), transition to single antiplatelet therapy for long-term secondary prevention. 1
Preferred Agents for Long-Term Therapy
- Clopidogrel 75 mg daily (preferred) 1, 3
- Aspirin 81 mg daily 1
- Aspirin 25 mg + extended-release dipyridamole 200 mg twice daily (alternative) 1, 3
Clopidogrel or aspirin/extended-release dipyridamole are preferred over aspirin alone for long-term secondary prevention in non-cardioembolic stroke. 3
Special Clinical Scenarios
Intracranial Atherosclerotic Disease (ICAD)
For patients with symptomatic moderate-to-severe intracranial stenosis (50-99%), DAPT with aspirin and clopidogrel is recommended over single antiplatelet therapy. 1 This should be combined with:
- Systolic blood pressure target <140 mmHg 1
- High-dose statin therapy 1
- At least moderate physical activity 1
Angioplasty and stenting are NOT recommended; DAPT is the appropriate medical therapy. 1
Embolic Stroke of Undetermined Source (ESUS)
Patients with ESUS should receive antiplatelet therapy, NOT oral anticoagulants. 1, 3 Use standard single antiplatelet regimens as outlined above.
Extracranial Artery Dissection
Either antiplatelet therapy or oral anticoagulation is acceptable for at least 3 months. 1 The choice depends on individual bleeding risk and anatomic considerations.
Other Specific Etiologies
- Carotid web: Antiplatelet therapy recommended 1
- Fibromuscular dysplasia: Antiplatelet therapy plus lifestyle modification 1
- Positive antiphospholipid antibodies (without APS): Antiplatelet therapy 1
Critical Safety Considerations
Bleeding Risk Management
Key contraindications to antiplatelet therapy:
- Active pathological bleeding (peptic ulcer, intracranial hemorrhage) 4
- For clopidogrel specifically: hypersensitivity to the drug 4
Factors increasing bleeding risk with DAPT:
- Body weight <60 kg (consider clopidogrel 5 mg maintenance dose instead of 10 mg for prasugrel, though this applies to ACS, not stroke) 5
- Age ≥75 years 5
- Concomitant use of anticoagulants, NSAIDs, SSRIs, or SNRIs 4
The risk of moderate-to-severe bleeding with DAPT is approximately 0.7-1.5%, compared to 0.3-0.8% with aspirin alone, but this risk does not significantly vary by timing of initiation within 72 hours. 2
CYP2C19 Considerations
Clopidogrel effectiveness depends on CYP2C19 metabolism. 4 Patients who are CYP2C19 poor metabolizers have reduced conversion to active metabolite and diminished antiplatelet effect. 4 Consider alternative P2Y12 inhibitors in identified poor metabolizers. 4
Avoid concomitant use of clopidogrel with omeprazole or esomeprazole, as these CYP2C19 inhibitors reduce clopidogrel's effectiveness. 4
Premature Discontinuation
Discontinuing antiplatelet therapy prematurely, particularly in the first few weeks after acute stroke, increases the risk of subsequent cardiovascular events. 5 If surgery is required, discontinue clopidogrel at least 5 days prior to procedures with major bleeding risk. 4
Common Pitfalls to Avoid
Do not delay aspirin beyond 48 hours in patients not receiving thrombolysis—early administration (within 24-48 hours) reduces early recurrent stroke and improves long-term outcomes. 1, 6
Do not continue DAPT beyond 21-30 days in minor stroke/TIA patients—prolonged DAPT increases bleeding risk without additional benefit. 7
Do not use DAPT as first-line therapy in moderate-to-severe stroke—the evidence supports DAPT only for minor stroke (NIHSS ≤3-5) and high-risk TIA. 1
Do not forget to exclude intracranial hemorrhage before initiating any antiplatelet therapy. 1
Do not use anticoagulation in ESUS—multiple trials have shown no benefit over antiplatelet therapy. 1, 3