What are the recommended antithrombotic therapies for patients with ischemic stroke?

Recommended Antithrombotic Therapies for Ischemic Stroke

For patients with ischemic stroke, the recommended antithrombotic therapy depends on stroke etiology, with antiplatelet agents for noncardioembolic strokes and oral anticoagulation for cardioembolic strokes, particularly those associated with atrial fibrillation.

Acute Management of Ischemic Stroke

Initial Therapy

• For patients with acute ischemic stroke or TIA, early aspirin therapy (within 48 hours) at a dose of 160-325 mg is strongly recommended over no aspirin therapy or parenteral anticoagulation (Grade 1A) 1
• IV recombinant tissue plasminogen activator (r-tPA) is recommended for eligible patients within 3 hours of symptom onset (Grade 1A) 1
• For patients with restricted mobility, prophylactic-dose subcutaneous heparin (LMWH preferred over UFH) or intermittent pneumatic compression devices are suggested (Grade 2B) 1

Long-Term Secondary Prevention Based on Stroke Etiology

Noncardioembolic Stroke (Atherothrombotic, Small Vessel Disease)

• Antiplatelet therapy is recommended with one of the following options 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)

• Of these options, clopidogrel or aspirin/extended-release dipyridamole are suggested over aspirin (Grade 2B) or cilostazol (Grade 2C) 1

• Avoid combination therapy with clopidogrel plus aspirin for long-term use as it increases bleeding risk without additional benefit (Grade 1B) 1

• For high-risk TIA or minor stroke, short-term dual antiplatelet therapy (aspirin plus clopidogrel) for 21-30 days may be beneficial when started within 24 hours of symptom onset 2

Cardioembolic Stroke (Atrial Fibrillation)

• Oral anticoagulation is strongly recommended over no antithrombotic therapy (Grade 1A), aspirin (Grade 1B), or combination therapy with aspirin and clopidogrel (Grade 1B) 1

• For patients with atrial fibrillation (including paroxysmal AF):

  • Dabigatran 150 mg twice daily is suggested over vitamin K antagonists (Grade 2B) 1
  • DOACs (apixaban, dabigatran, edoxaban, rivaroxaban) are generally preferred over warfarin due to lower risk of intracranial hemorrhage 2
  • Target INR for warfarin is 2.0-3.0 1, 3

• Timing of anticoagulation initiation:

  • For TIA: Start immediately
  • For mild stroke (NIHSS <8): Start 1-3 days after event
  • For moderate stroke (NIHSS 8-15): Start 6 days after event
  • For severe stroke (NIHSS ≥16): Start 12 days after event 2

• For patients unsuitable for oral anticoagulation, combination therapy with aspirin and clopidogrel is recommended over aspirin alone (Grade 1B) 1

Special Considerations

Mechanical Heart Valves

• Warfarin is required (DOACs are contraindicated) 2, 3
• Target INR varies by valve type and position:
  • St. Jude bileaflet valve in aortic position: INR 2.0-3.0
  • Tilting disk valves and bileaflet valves in mitral position: INR 2.5-3.5
  • Caged ball or caged disk valves: INR 2.5-3.5 plus aspirin 75-100 mg/day 3

Renal Impairment

• Dabigatran is contraindicated in severe renal impairment (CrCl ≤30 mL/min) 1, 2
• Regular assessment of renal function is necessary for patients on DOACs 2

Intracerebral Hemorrhage History

• For patients with a history of symptomatic primary intracerebral hemorrhage, antithrombotic therapy for ischemic stroke prevention is generally not recommended (Grade 2C) 1
• Patients with cerebral amyloid angiopathy or lobar ICH should avoid anticoagulation due to high recurrent ICH risk 2
• For patients with deep hemorrhages at lower risk of recurrent ICH but high thromboembolic risk (e.g., mechanical heart valves or CHADS₂ score ≥4), anticoagulation may be considered 1

Monitoring and Follow-up

• INR monitoring for patients on warfarin (target 2.0-3.0) 2, 3
• Regular assessment of renal function for patients on DOACs 2
• Medication adherence evaluation at each visit 2
• Consider left atrial appendage occlusion for patients with high bleeding risk who cannot tolerate long-term anticoagulation 2

Common Pitfalls and Caveats

• Avoid combining antiplatelet and anticoagulant therapy unless specifically indicated, as this substantially increases bleeding risk 2
• DOACs are contraindicated in patients with mechanical heart valves or moderate to severe mitral stenosis 2
• Delaying anticoagulation should be considered for patients at high risk of hemorrhagic complications (e.g., those with extensive infarct burden or evidence of significant hemorrhagic transformation) 1
• For patients transitioning to oral anticoagulation, bridge with aspirin until therapeutic anticoagulation is achieved 1