Medications for Acute Ischemic Stroke Patients Not Eligible for tPA
For patients with acute ischemic stroke who are not candidates for thrombolysis, start aspirin 160-325 mg orally within 48 hours of symptom onset after brain imaging excludes hemorrhage. 1
Immediate Antiplatelet Therapy
Initiate aspirin 160-325 mg as a loading dose within 48 hours of stroke onset for all patients not receiving thrombolysis, after confirming absence of intracranial hemorrhage on neuroimaging 1, 2
This early aspirin therapy (Grade 1A recommendation) reduces the risk of death and dependency, and decreases early recurrent ischemic stroke without major hemorrhagic complications 1, 3
Aspirin can be administered orally, by nasogastric tube, or per rectum in patients who cannot swallow 3
Venous Thromboembolism Prophylaxis
For patients with restricted mobility, initiate prophylactic-dose subcutaneous heparin or intermittent pneumatic compression devices (Grade 2B) 1
Low-molecular-weight heparin (LMWH) is preferred over unfractionated heparin for VTE prophylaxis 4
Avoid elastic compression stockings (Grade 2B recommendation against their use) 1
Special Considerations for Dual Antiplatelet Therapy
For patients with minor ischemic stroke (NIHSS ≤3) or high-risk TIA (ABCD2 ≥4), consider dual antiplatelet therapy (aspirin plus clopidogrel) for 21 days, but only after confirming absence of hemorrhagic transformation on neuroimaging 5, 6
Dual antiplatelet therapy reduces recurrent stroke risk (RR 0.76) but increases major bleeding risk (RR 2.22) compared to aspirin alone 6
After 21 days of dual therapy, transition to long-term single antiplatelet therapy 5
Long-Term Secondary Prevention Strategy
For Noncardioembolic Stroke (atherothrombotic, lacunar, or cryptogenic):
Recommended antiplatelet options (Grade 1A): 1
- Aspirin 75-100 mg once daily
- Clopidogrel 75 mg once daily
- Aspirin/extended-release dipyridamole 25 mg/200 mg twice daily
- Cilostazol 100 mg twice daily
Preferred regimens: Clopidogrel or aspirin/extended-release dipyridamole are superior to aspirin monotherapy (Grade 2B) 1
Avoid long-term combination of aspirin plus clopidogrel (Grade 1B recommendation against) due to increased bleeding risk without proportional benefit 1, 7
For Cardioembolic Stroke (atrial fibrillation):
Initiate oral anticoagulation (target INR 2.0-3.0) over antiplatelet therapy (Grade 1B) 1
Timing of anticoagulation initiation depends on stroke severity: 5
- Mild stroke: >3 days after excluding hemorrhagic transformation
- Moderate stroke: >6-8 days after excluding hemorrhagic transformation
- Severe stroke: >12-14 days after excluding hemorrhagic transformation
Critical Pitfalls to Avoid
Do not delay aspirin therapy in patients outside the thrombolytic window unless hemorrhagic transformation is present 4
Do not initiate dual antiplatelet therapy before neuroimaging confirms absence of hemorrhagic transformation 5
Do not use therapeutic anticoagulation acutely instead of aspirin in the first 48 hours—aspirin is superior to therapeutic parenteral anticoagulation (Grade 1A) 1
Do not administer any antiplatelet therapy if hemorrhagic transformation is present until appropriate delay period (24-48 hours for HI1; 7-10 days for HI2, PH1, PH2) 5