What is the recommended anticoagulation therapy with warfarin or Direct Oral Anticoagulants (DOACs) after a stroke?

Anticoagulation After Stroke: DOACs vs Warfarin

For patients with nonvalvular atrial fibrillation and stroke, direct oral anticoagulants (DOACs) such as apixaban, dabigatran, edoxaban, or rivaroxaban are recommended over warfarin to reduce the risk of recurrent stroke. 1

Selection of Anticoagulant Based on Stroke Etiology

Nonvalvular Atrial Fibrillation

• First-line therapy: DOACs (apixaban, dabigatran, edoxaban, or rivaroxaban)

  • Lower risk of intracranial hemorrhage
  • No need for regular INR monitoring
  • Fewer drug-drug interactions 1
  • Better outcomes with 15.6 more days at home in the first year post-discharge compared to warfarin 2
  • 12% reduction in mortality risk compared to warfarin 2
  • Apixaban and edoxaban specifically show better prognosis after ischemic stroke than other DOACs 3

• Second-line therapy: Warfarin (target INR 2.0-3.0)

  • Use only if patient is unable to take DOACs 1
  • Higher risk of intracranial bleeding compared to DOACs 4

Valvular Atrial Fibrillation

• Mechanical valve replacement or moderate/severe mitral stenosis: Warfarin is mandatory (target INR 2.5-3.5) 1
  • DOACs should NOT be used in these patients 1
  • For mechanical mitral valve with prior stroke: Add aspirin 75-100 mg daily to warfarin (target INR 2.5-3.5) 1

Timing of Anticoagulation Initiation After Stroke

1. TIA with atrial fibrillation:

   • Initiate anticoagulation immediately 1

2. Stroke with LOW risk of hemorrhagic conversion:

   • May initiate anticoagulation 2-14 days after stroke 1

3. Stroke with HIGH risk of hemorrhagic conversion:

   • Delay anticoagulation beyond 14 days 1
   • Avoid heparinoids as bridging therapy in acute phase 1

Special Populations

End-Stage Renal Disease or Dialysis

• Warfarin or dose-adjusted apixaban may be reasonable 1
• Avoid dabigatran in severe renal impairment (CrCl ≤30 mL/min) 5

Patients with Contraindications to Lifelong Anticoagulation

• Consider left atrial appendage closure (Watchman device) if patient can tolerate at least 45 days of anticoagulation 1

Important Considerations and Pitfalls

1. Avoid combining anticoagulants with antiplatelets unless specifically indicated (e.g., mechanical valve), as this significantly increases bleeding risk 5

2. Monitor for specific bleeding risks:

   • DOACs have lower risk of intracranial bleeding but some (particularly dabigatran 150mg and rivaroxaban) have higher risk of gastrointestinal bleeding compared to warfarin 4
   • Apixaban 5mg twice daily has the most favorable bleeding profile among DOACs 4

3. Medication adherence is critical:

   • Unlike warfarin, there is no routine monitoring for DOACs
   • Missing doses leaves patients unprotected
   • Educate patients about the importance of strict adherence

4. Drug interactions:

   • Warfarin has numerous food and drug interactions
   • DOACs have fewer but still important interactions (e.g., with P-glycoprotein inhibitors/inducers)

5. Cost considerations:

   • DOACs are more expensive than warfarin but may be more cost-effective when considering monitoring costs and better outcomes 4

By following these evidence-based recommendations, clinicians can optimize anticoagulation therapy after stroke to reduce morbidity and mortality while minimizing bleeding risks.