What is the recommended antithrombotic therapy for acute post-ischemic stroke patients?

Antithrombotic Therapy for Acute Post-Ischemic Stroke

Start aspirin 160-325 mg within 48 hours of symptom onset for all acute ischemic stroke patients, unless they have evidence of hemorrhagic transformation or are candidates for dual antiplatelet therapy. 1, 2

Immediate Management (First 48 Hours)

Standard Antiplatelet Therapy

• Aspirin monotherapy (160-325 mg) is the cornerstone of acute treatment, initiated within 48 hours of stroke onset 1, 2, 3
• This approach prevents approximately 10 deaths and early recurrent strokes per 1,000 patients treated 3
• Aspirin is preferred over therapeutic parenteral anticoagulation in the acute phase 2

Dual Antiplatelet Therapy for High-Risk Patients

For minor ischemic stroke or high-risk TIA, initiate dual antiplatelet therapy with aspirin 81 mg plus clopidogrel 75 mg (with 300-600 mg loading dose) within 12-24 hours of symptom onset. 2, 4

• Recent high-quality evidence from 2023 demonstrates that dual antiplatelet therapy initiated within 72 hours reduces new stroke risk (7.3% vs 9.2%, HR 0.79,95% CI 0.66-0.94) 4
• The trade-off is a modest increase in moderate-to-severe bleeding (0.9% vs 0.4%, HR 2.08) 4
• Continue dual therapy for 21 days, then transition to monotherapy 2, 5

Contraindications to Immediate Antiplatelet Therapy

Absolute Contraindications

• Active intracranial hemorrhage or primary hemorrhagic stroke 1
• Severe hemorrhagic transformation (HI2, PH1, PH2 classification) 1
• Evidence of significant hemorrhage on neuroimaging 1

Timing Modifications Based on Stroke Characteristics

• Large ischemic strokes: Delay anticoagulation for 5-7 days until hemorrhagic transformation risk decreases 1
• Minor hemorrhagic transformation (HI1): May initiate antiplatelet therapy within 24-48 hours after confirming no progression 1
• Severe hemorrhagic transformation: Delay anticoagulation for 7-10 days 1

Post-Thrombolysis Considerations

• Delay antithrombotic therapy for 24 hours after IV thrombolysis 5
• No definitive guidelines exist for the period immediately after mechanical thrombectomy, but clinical practice typically mirrors the post-thrombolysis approach 5

VTE Prophylaxis in Immobilized Patients

Preferred Approach

• Use prophylactic-dose LMWH over unfractionated heparin for patients with restricted mobility 1
• Alternatively, apply intermittent pneumatic compression devices within 24 hours of admission 1
• Do not use elastic compression stockings alone - they are ineffective for VTE prophylaxis 6, 1

Timing for VTE Prophylaxis

• Start prophylactic anticoagulation once hemorrhagic transformation risk is assessed and deemed acceptable 1
• For patients with large infarcts, delay until imaging confirms stability (typically 2-4 days) 1

Long-Term Secondary Prevention (Beyond Acute Phase)

Non-Cardioembolic Stroke

Transition to long-term monotherapy with clopidogrel 75 mg daily or aspirin/extended-release dipyridamole 25/200 mg twice daily after completing the acute dual antiplatelet period. 6, 2

• Clopidogrel or aspirin/extended-release dipyridamole are preferred over aspirin monotherapy for long-term prevention 6, 2
• Cilostazol 100 mg twice daily is an alternative but less preferred option 6

Cardioembolic Stroke with Atrial Fibrillation

Initiate oral anticoagulation within 1-2 weeks after stroke onset for patients with atrial fibrillation. 6

• Oral anticoagulation is superior to aspirin, aspirin plus clopidogrel, or no therapy 6, 2
• Bridge with aspirin until therapeutic anticoagulation is achieved 6
• Earlier anticoagulation (within days) can be considered for small infarcts without hemorrhage on imaging 6
• Delay anticoagulation for extensive infarcts or significant hemorrhagic transformation 6

Critical Pitfalls to Avoid

• Do not extend dual antiplatelet therapy beyond 3 months - bleeding risks substantially increase 5, 7
• Do not use antiplatelet therapy in cardioembolic stroke - these patients require anticoagulation, and antiplatelets may increase hemorrhagic risk without preventing cardioembolic recurrence 5
• Do not use therapeutic-dose anticoagulation in acute ischemic stroke unless there is a compelling cardioembolic indication, and even then, timing must be carefully considered 2
• Do not prescribe dabigatran if creatinine clearance is ≤30 mL/min - it is contraindicated in severe renal impairment 6, 2