Medications for Acute to Subacute Ischemic Stroke
Primary Recommendation
Start aspirin 160-325 mg orally within 24-48 hours of stroke onset after CT/MRI excludes hemorrhage—this is the cornerstone of acute ischemic stroke pharmacotherapy and reduces early recurrent stroke, mortality, and morbidity. 1, 2
Antiplatelet Therapy Algorithm
For Most Acute Ischemic Strokes (Moderate to Severe, NIHSS >3)
Aspirin monotherapy is the standard:
- Initiate aspirin 160-325 mg within 24-48 hours after symptom onset once brain imaging excludes hemorrhage 1, 2, 3
- This prevents approximately 9 deaths or recurrent strokes per 1,000 patients treated 4
- The primary benefit is reduction of early recurrent ischemic stroke, not limitation of initial stroke damage 2
- Class I, Level of Evidence A recommendation from the American Heart Association 2
Critical timing considerations:
- If the patient received IV thrombolysis (rtPA), delay aspirin for 24 hours after thrombolysis and after repeat imaging excludes hemorrhage 3
- Aspirin as adjunctive therapy within 24 hours of thrombolytic therapy is contraindicated (Class III, Level of Evidence A) due to increased bleeding risk 1, 2
Alternative routes if swallowing impaired:
For Minor Stroke (NIHSS ≤3) or High-Risk TIA (ABCD2 ≥4)
Dual antiplatelet therapy (DAPT) is recommended:
- Initiate aspirin plus clopidogrel within 24 hours of symptom onset 1
- Loading dose: clopidogrel 300 mg plus aspirin 160-325 mg on day 1 5
- Maintenance: clopidogrel 75 mg plus aspirin 100 mg daily 5
- Duration: 21 days only, then transition to single antiplatelet therapy 1
- This regimen reduces new stroke risk even when initiated up to 72 hours after onset (5.8% vs 8.2% with aspirin alone, HR 0.70) 5
Important restriction:
- DAPT is NOT recommended for routine treatment of all acute ischemic strokes (Class III, Level of Evidence C) 1, 2
- Clopidogrel monotherapy for acute stroke has uncertain benefit (Class IIb, Level of Evidence C) 2
Blood Pressure Management
Permissive hypertension is the default approach:
- Maintain blood pressure <180/105 mmHg during first 24 hours after acute reperfusion treatment 3
- For extremely high BP (>220/120 mmHg), reduce cautiously by no more than 10-20% 3
- Avoid aggressive BP lowering—sudden drops can cause neurological deterioration 6
Additional Acute Management Medications
Anticoagulation considerations:
- Routine anticoagulation (IV heparin) is NOT recommended for unselected acute ischemic stroke patients 3
- Low-dose heparin may be justified for specific high-risk situations: emboligenic heart disease, tight carotid stenosis, or high pulmonary embolism risk 6
- For intracerebral hemorrhage, reverse anticoagulation immediately with 4-factor prothrombin complex concentrate (preferred over fresh-frozen plasma) for INR ≥2.0 3
Supportive medications:
- Intermittent pneumatic compression devices for immobile patients 3
- Oxygen therapy, antibiotics, paracetamol, insulin, and anticonvulsants only for specific complications 6
Long-Term Transition (Subacute Phase)
After initial 21-48 hours:
- Transition to maintenance aspirin 75-162 mg daily for long-term secondary prevention 3
- Lower doses (75-100 mg) have similar efficacy with fewer gastrointestinal side effects compared to higher doses 2
- If aspirin not tolerated, clopidogrel 75 mg daily is an alternative 3
Critical Pitfalls to Avoid
Never use aspirin as a substitute for IV rtPA in eligible patients 2, 3—thrombolysis takes priority when indicated
Never administer aspirin within 24 hours of thrombolytic therapy—this significantly increases hemorrhagic transformation risk 1, 2, 3
Never use IV glycoprotein IIb/IIIa inhibitors outside clinical trials—not recommended by guidelines 2
Never continue DAPT beyond 21-90 days in most patients—long-term dual therapy increases bleeding without clear benefit 2