Pharmacotherapy for Ischemic Stroke
For acute ischemic stroke, intravenous recombinant tissue plasminogen activator (r-tPA) should be administered within 3 hours of symptom onset (Grade 1A) or within 4.5 hours in selected cases (Grade 2C), followed by early aspirin therapy (160-325 mg) within 48 hours. 1
Acute Phase Management
Thrombolytic Therapy
- IV r-tPA is recommended if treatment can be initiated within 3 hours of symptom onset (Grade 1A) 1
- IV r-tPA may be considered if treatment can be initiated within 4.5 hours but not within 3 hours of symptom onset (Grade 2C) 1
- IV r-tPA should not be administered if treatment cannot be initiated within 4.5 hours of symptom onset (Grade 1B) 1
- For patients with proximal cerebral artery occlusions who don't meet eligibility criteria for IV r-tPA, intraarterial r-tPA initiated within 6 hours of symptom onset may be considered (Grade 2C) 1
Antiplatelet Therapy
- Early aspirin therapy (160-325 mg) should be started within 48 hours of symptom onset (Grade 1A) 1
- Aspirin is preferred over therapeutic parenteral anticoagulation in the acute phase (Grade 1A) 1
- For patients with impaired swallowing, rectal aspirin or administration via nasogastric tube is appropriate 2, 3
- Aspirin reduces early recurrent ischemic stroke without major risk of hemorrhagic complications and improves long-term outcomes 3, 4
Venous Thromboembolism Prophylaxis
- For patients with restricted mobility, prophylactic-dose subcutaneous heparin (UFH or LMWH) or intermittent pneumatic compression devices are recommended (Grade 2B) 1
- Prophylactic-dose LMWH is preferred over prophylactic-dose UFH (Grade 2B) 1
- Elastic compression stockings should be avoided in patients with primary intracerebral hemorrhage and restricted mobility (Grade 2B) 1
Long-term Secondary Prevention
For Non-cardioembolic Stroke
- Long-term antiplatelet therapy is recommended with one of the following (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)
- Clopidogrel or aspirin/extended-release dipyridamole are preferred over aspirin (Grade 2B) or cilostazol (Grade 2C) 1
- The combination of clopidogrel plus aspirin is not recommended for long-term secondary prevention due to increased bleeding risk (Grade 1B) 1, 5
For Minor Stroke or High-risk TIA
- For minor ischemic stroke (NIHSS ≤3) or high-risk TIA (ABCD2 ≥4), dual antiplatelet therapy (DAPT) with aspirin 81 mg daily and clopidogrel 75 mg daily should be initiated early, ideally within 12-24 hours of symptom onset 1
- A loading dose of aspirin (160-325 mg) and clopidogrel (300-600 mg) should be given at the beginning of DAPT therapy 1
- DAPT should be continued for 21 days, then switched to single antiplatelet therapy for long-term prevention 1
For Cardioembolic Stroke (with Atrial Fibrillation)
- Oral anticoagulation is recommended over no antithrombotic therapy (Grade 1A), aspirin (Grade 1B), or combination therapy with aspirin and clopidogrel (Grade 1B) 1
- Oral anticoagulation with dabigatran 150 mg twice daily may be preferred over adjusted-dose vitamin K antagonist therapy (Grade 2B) 1
- Oral anticoagulation should generally be initiated within 1-2 weeks after stroke onset 1
- Earlier anticoagulation can be considered for patients at low risk of bleeding complications 1
- Delaying anticoagulation should be considered for patients at high risk of hemorrhagic complications 1
- Patients should be bridged with aspirin until anticoagulation reaches a therapeutic level 1
Special Considerations
- Dabigatran is contraindicated in patients with severe renal impairment (estimated creatinine clearance ≤30 mL/min) 1
- For patients with embolic stroke of undetermined source (ESUS), antiplatelet therapy is recommended rather than oral anticoagulants 1
- The benefit of clopidogrel over aspirin in preventing major vascular events with long-term use (>5 years) may be offset by a reduction in cancer-related mortality with regimens containing aspirin 1