What is the management of a patient who experiences a stroke while on Eliquis (apixaban)?

Management of Stroke While on Apixaban (Eliquis)

For patients who experience a stroke while on apixaban, management should include temporarily discontinuing apixaban and timing its resumption based on stroke size, with endovascular thrombectomy as the preferred acute intervention for large vessel occlusions.

Acute Management

Initial Assessment

• Determine last dose of apixaban
• Assess stroke severity using NIHSS (National Institutes of Health Stroke Scale)
• Perform urgent neuroimaging (CT or MRI) to confirm ischemic stroke and rule out hemorrhage
• Evaluate for large vessel occlusion that might benefit from mechanical thrombectomy

Thrombolytic Therapy Considerations

• Thrombolysis (rtPA) is generally contraindicated in patients on apixaban if:
  • Last dose was within 48 hours 1
  • Apixaban levels are ≥30 ng/mL (if testing available) 1
  • INR is above 1.7 (although standard coagulation tests don't reliably assess apixaban's effect) 2

Endovascular Treatment

• Endovascular thrombectomy is the preferred first-line treatment for patients with large vessel occlusion who are on apixaban 1
• This approach is supported by European Stroke Organization and European Heart Rhythm Association recommendations for patients with contraindications to thrombolysis 1

Post-Acute Management and Anticoagulation Resumption

Timing of Apixaban Resumption

The timing of resuming apixaban depends on stroke size:

1. Transient Ischemic Attack (TIA):

   • Resume apixaban at day 0-3 3

2. Small-sized stroke (<1.5 cm):

   • Resume apixaban at day 3-5 3

3. Medium-sized stroke (≥1.5 cm, excluding full cortical territory):

   • Resume apixaban at day 7-9 3

4. Large stroke or stroke with hemorrhagic transformation:

   • Delay resumption for 14 days after stroke onset 2
   • Consider repeat brain imaging before restarting anticoagulation 2

Bridging Considerations

• There is generally no need for bridging with heparin or LMWH when restarting apixaban 2
• In very high thrombotic risk patients, individualized bridging decisions may be needed 2

Evaluation of Stroke Etiology

Assess for Potential Causes of Anticoagulation Failure

• Medication non-adherence
• Drug-drug interactions affecting apixaban levels (P-glycoprotein inhibitors, CYP3A4 inhibitors) 2
• Incorrect dosing (standard dose is 5 mg twice daily; reduced to 2.5 mg twice daily for patients with ≥2 of: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL) 4
• Presence of cerebral atherosclerosis (may increase recurrent stroke risk even with appropriate anticoagulation) 5

Consider Alternative Anticoagulation

• If stroke occurs despite proper adherence to apixaban, consider switching to another anticoagulant 2
• The European Society of Cardiology guidelines suggest that switching to another anticoagulant should be considered if a patient suffers a stroke while taking an anticoagulant 2

Long-term Management

Monitoring and Follow-up

• Regular assessment of renal function (apixaban dosing depends partly on renal function) 4
• Evaluate for and manage vascular risk factors (hypertension, diabetes, hyperlipidemia)
• Consider adding antiplatelet therapy only in specific situations (e.g., recent coronary stenting), as combination therapy increases bleeding risk 2

Important Caveats

• Avoid combination therapy of apixaban with antiplatelet agents for long-term stroke prevention, as this significantly increases bleeding risk without clear benefit 2
• Early initiation of apixaban after stroke appears to have a favorable safety profile compared to delayed warfarin initiation, with potentially lower rates of recurrent strokes and fatal outcomes 3
• Patients with cerebral atherosclerosis may have higher rates of recurrent events despite appropriate anticoagulation (4.6% vs 1.7% in those without atherosclerosis) 5

The AREST trial suggests that early initiation of apixaban after TIA or small to medium-sized stroke is relatively safe and may be more effective than delayed anticoagulation with warfarin, though larger studies are needed to confirm these findings 3.