When to start Eliquis (apixaban) in a patient with embolic stroke?

Timing of Apixaban Initiation After Embolic Stroke

For patients with embolic stroke due to atrial fibrillation, apixaban should be initiated based on infarct size: 0-3 days for TIA, 3-5 days for small infarcts (<1.5 cm), 7-9 days for medium infarcts (≥1.5 cm but less than full cortical territory), and after 14 days for large infarcts. 1

Evidence-Based Timing Algorithm

The timing of anticoagulation after an embolic stroke requires balancing the risk of recurrent stroke against the risk of hemorrhagic transformation. The 2021 AHA/ASA guidelines provide specific recommendations based on hemorrhagic risk:

• High risk of hemorrhagic conversion: Delay anticoagulation beyond 14 days 1
• Low risk of hemorrhagic conversion: May initiate anticoagulation 2-14 days after stroke 1
• TIA: Reasonable to initiate anticoagulation immediately (within 48 hours) 1

Stratification by Infarct Size

Recent evidence supports a more nuanced approach based on infarct size:

1. TIA: Start apixaban at day 0-3 2, 3
2. Small infarct (<1.5 cm): Start apixaban at day 3-5 2, 3
3. Medium infarct (≥1.5 cm but less than full cortical territory): Start apixaban at day 7-9 2, 3
4. Large infarct (full cortical territory): Start apixaban after 14 days 1, 3

Rationale and Supporting Evidence

The 2021 AHA/ASA guidelines (Class 2a, Level B-NR) recommend delaying anticoagulation beyond 14 days in patients at high risk of hemorrhagic conversion 1. However, more recent studies suggest that earlier initiation may be safe in selected patients.

The AREST trial found that early apixaban initiation based on stroke size did not increase symptomatic hemorrhagic transformation compared to later warfarin initiation 2. In fact, there were numerically fewer recurrent strokes/TIAs (14.6% vs 19.2%) and no symptomatic intracerebral hemorrhages in the early apixaban group 2.

A 2024 study demonstrated that early initiation of apixaban tailored to infarct size was associated with:

• Better functional outcomes (61.8% vs 48.1% achieving mRS ≤2)
• Lower rates of stroke progression or early recurrence (4.7% vs 13.2%)
• No increase in symptomatic hemorrhagic transformation 3

Clinical Implementation

1. Assess infarct size using brain imaging (CT or MRI)

2. Evaluate hemorrhagic risk factors:

   • Large infarct volume
   • Evidence of hemorrhagic transformation on initial imaging
   • Severe stroke (NIHSS >15)
   • Uncontrolled hypertension
   • Advanced age (>80 years)
   • Prior ICH history

3. Follow the "1-3-6-12 day rule" as suggested by European guidelines 1:

   • TIA: 1 day
   • Small, non-disabling infarct: 3 days
   • Moderate stroke: 6 days
   • Large infarcts: 12-14 days

Important Considerations

• Apixaban is preferred over warfarin for patients with non-valvular AF and stroke/TIA (Class 1, Level B-R) 1
• No bridging with heparin is needed when starting apixaban 1
• Monitor closely for signs of neurological deterioration which could indicate hemorrhagic transformation
• Repeat brain imaging before starting anticoagulation in patients with moderate to large infarcts to exclude hemorrhagic transformation

Common Pitfalls to Avoid

• Delaying anticoagulation unnecessarily in patients with TIA or small infarcts increases the risk of recurrent embolic events
• Starting too early in patients with large infarcts increases hemorrhagic transformation risk
• Failing to exclude hemorrhagic transformation before initiating anticoagulation in moderate to large strokes
• Not considering patient-specific factors like age, renal function, and concomitant medications that might affect bleeding risk

By following this evidence-based approach to timing apixaban initiation after embolic stroke, you can optimize the balance between preventing recurrent strokes and avoiding hemorrhagic complications.