Initial Antiplatelet Therapy for Ischemic Stroke
For patients with acute ischemic stroke, early aspirin therapy at a dose of 160-325 mg should be administered within 48 hours of symptom onset after intracranial hemorrhage is ruled out on neuroimaging studies. 1
Initial Antiplatelet Management Algorithm
For All Acute Ischemic Stroke Patients:
- Administer aspirin 160-325 mg as a single loading dose after excluding intracranial hemorrhage on neuroimaging 1
- If swallowing is impaired, options include:
- Rectal aspirin 325 mg daily
- Aspirin 81 mg daily via enteral tube
- Clopidogrel 75 mg daily via enteral tube 1
For Minor Ischemic Stroke (NIHSS ≤3) or High-Risk TIA (ABCD2 ≥4):
- Dual antiplatelet therapy (DAPT) should be initiated as early as possible, ideally within 12-24 hours of symptom onset 1
- DAPT regimen:
- Loading dose: Aspirin 160-325 mg + Clopidogrel 300-600 mg
- Maintenance: Aspirin 81 mg daily + Clopidogrel 75 mg daily
- Duration: 21 days, then switch to single antiplatelet therapy 1
For Mild-Moderate Ischemic Stroke (NIHSS ≤5) or High-Risk TIA (ABCD2 ≥4):
- Alternative DAPT regimen:
- Loading dose: Aspirin 300-325 mg + Ticagrelor 180 mg
- Maintenance: Aspirin 75-100 mg daily + Ticagrelor 90 mg twice daily
- Duration: 30 days, then switch to single antiplatelet therapy 1
Long-Term Antiplatelet Therapy
After the initial treatment period, patients with non-cardioembolic ischemic stroke should transition to long-term single antiplatelet therapy with one of the following options:
- Aspirin 75-100 mg daily
- Clopidogrel 75 mg daily
- Aspirin/extended-release dipyridamole 25/200 mg twice daily
- Cilostazol 100 mg twice daily 1, 2
Of these options, clopidogrel or aspirin/extended-release dipyridamole are preferred over aspirin alone or cilostazol 1, 2.
Special Considerations
Intracranial Atherosclerotic Stenosis
- For patients with moderate to high-grade intracranial atherosclerotic stenosis (50-99%), dual antiplatelet therapy is appropriate as medical therapy 1
- Angioplasty and stenting are not recommended for these patients 1
Embolic Stroke of Undetermined Source (ESUS)
- Antiplatelet therapy is recommended rather than oral anticoagulation 1
Atrial Fibrillation
Clinical Evidence and Rationale
The recommendation for early aspirin therapy is supported by high-quality evidence showing that aspirin started within 48 hours of stroke onset reduces death and dependency by preventing early recurrent ischemic stroke without significantly increasing the risk of hemorrhagic complications 3, 4.
Recent evidence from the INSPIRES trial demonstrates that dual antiplatelet therapy with clopidogrel plus aspirin initiated within 72 hours after stroke onset leads to a lower risk of new stroke at 90 days compared to aspirin alone (7.3% vs 9.2%), though with a slightly higher risk of moderate-to-severe bleeding (0.9% vs 0.4%) 5.
The short-term use of dual antiplatelet therapy in specific stroke subtypes (minor stroke or high-risk TIA) is supported by multiple trials showing reduction in recurrent ischemic events, but this benefit must be balanced against the increased bleeding risk when extended beyond 21-30 days 6.
Common Pitfalls and Caveats
Timing is critical: Delaying antiplatelet therapy beyond 48 hours reduces its effectiveness in preventing early recurrent stroke.
Neuroimaging first: Always rule out intracranial hemorrhage before initiating antiplatelet therapy.
Dual antiplatelet duration: Extending dual antiplatelet therapy beyond the recommended 21-30 days increases bleeding risk without additional benefit.
Loading doses: Consider loading doses (aspirin 160-325 mg, clopidogrel 300-600 mg) for rapid platelet inhibition in high-risk patients 7.
Avoid therapeutic anticoagulation: Early therapeutic parenteral anticoagulation is not recommended over aspirin in acute ischemic stroke 1, 2.
DVT prophylaxis: For patients with restricted mobility, prophylactic-dose heparin or intermittent pneumatic compression devices should be used 1, 2.