Is apixaban (eliquis) safe for patients with a history of hemorrhagic stroke?

Apixaban Safety in Patients with History of Hemorrhagic Stroke

Apixaban (Eliquis) should generally be avoided in patients with a history of hemorrhagic stroke due to the significantly increased risk of recurrent intracerebral hemorrhage. 1

Risk Assessment for Anticoagulation After Hemorrhagic Stroke

When considering anticoagulation in patients with a history of hemorrhagic stroke, several factors must be carefully evaluated:

Risk Factors for Recurrent Hemorrhage

• Lobar location of initial hemorrhagic stroke
• Older age
• Presence and number of microbleeds on gradient echo MRI
• Ongoing anticoagulation
• Presence of cerebral amyloid angiopathy 1

Timing Considerations

The optimal timing for resumption of anticoagulation after intracerebral hemorrhage (ICH) is uncertain, with no randomized trial data available to guide this decision. However, observational data suggests:

• The risk of rebleeding with early resumption of anticoagulation exceeds the risk of thromboembolism from withholding it
• A survival model found that total risk of ischemic plus hemorrhagic stroke was minimized when anticoagulation was reinitiated after approximately 10 weeks
• A delay of at least 1 month after ICH is suggested 1

Alternative Approaches for Patients with AF and History of Hemorrhagic Stroke

For patients with atrial fibrillation who have had a hemorrhagic stroke but require stroke prevention:

1. Left atrial appendage closure: Percutaneous left atrial appendage closure (Watchman device) might be a safer alternative to warfarin in some patients with atrial fibrillation 1, 2

2. Antiplatelet therapy: Antiplatelet monotherapy may be a safer alternative to oral anticoagulation in selected patients, though it provides less protection against cardioembolic events 1

3. Risk-benefit assessment: The decision must weigh the risk of recurrent hemorrhage against the risk of cardioembolic events, particularly in patients with high CHA₂DS₂-VASc scores 1

Apixaban vs. Warfarin in Patients with Bleeding History

While apixaban has a better safety profile than warfarin in terms of intracranial hemorrhage risk:

• Apixaban was associated with lower rates of hemorrhagic stroke compared to warfarin (0.24% vs 0.47% per year) in the ARISTOTLE trial 1, 3
• In patients with a history of bleeding, apixaban still demonstrated fewer outcomes compared to warfarin for stroke, hemorrhagic stroke, death, or major bleeding 4
• However, this data did not specifically focus on patients with prior hemorrhagic stroke

Clinical Decision-Making Algorithm

1. Assess hemorrhagic stroke characteristics:

   • Location (lobar vs. deep)
   • Time since hemorrhage (minimum 4-8 weeks)
   • Presence of microbleeds on MRI
   • Underlying cause (hypertension, amyloid angiopathy, etc.)

2. Evaluate competing risks:

   • CHA₂DS₂-VASc score for stroke risk
   • HAS-BLED score for bleeding risk
   • Presence of cerebral atherosclerosis (may increase recurrent stroke risk) 5

3. Consider alternatives to full anticoagulation:

   • Left atrial appendage closure if patient can tolerate 45 days of anticoagulation 2
   • Antiplatelet therapy if stroke risk is moderate
   • No antithrombotic therapy if bleeding risk substantially exceeds stroke risk

Important Caveats and Pitfalls

• The safety of oral anticoagulation in patients with cerebral amyloid angiopathy and in the presence of microbleeds remains unclear 1
• Avoid combining anticoagulants with antiplatelets unless specifically indicated, as this significantly increases bleeding risk 2
• While DOACs (including apixaban) have lower rates of intracranial hemorrhage than warfarin, their safety specifically in patients with prior hemorrhagic stroke has not been well established 1
• The timing of anticoagulation initiation after ischemic stroke varies based on stroke severity, but hemorrhagic stroke presents a much higher risk profile 2

In conclusion, while apixaban has a better safety profile than warfarin regarding intracranial hemorrhage, a history of hemorrhagic stroke remains a significant concern for any anticoagulant therapy. Left atrial appendage closure or careful antiplatelet therapy may be safer alternatives in this high-risk population.