Is Warfarin (Coumadin) preferable over Apixaban (Eliquis)?

Apixaban (Eliquis) Is Superior to Warfarin (Coumadin) for Most Patients with Atrial Fibrillation

Apixaban is generally superior to warfarin for stroke prevention in nonvalvular atrial fibrillation, with significantly fewer overall strokes, major bleeding events, and lower mortality rates. 1

Comparative Efficacy and Safety

Efficacy

• In the ARISTOTLE trial, apixaban demonstrated:
  • 21% reduction in stroke or systemic embolism compared to warfarin (1.27% vs 1.60% per year) 1, 2
  • Significant reduction in hemorrhagic stroke (0.24% vs 0.47%) 1
  • Similar rates of ischemic stroke 1
  • 11% reduction in all-cause mortality 1, 2

Safety Profile

• Apixaban shows a superior safety profile:
  • 31% reduction in major bleeding compared to warfarin (2.13% vs 3.09%) 1
  • 49% reduction in intracranial hemorrhage 1, 2
  • Similar rates of gastrointestinal bleeding (unlike other NOACs which increase this risk) 1
  • In real-world studies, apixaban had a 48% lower risk of major bleeding compared to warfarin 3

Advantages of Apixaban Over Warfarin

1. Predictable Pharmacology:

   • No routine coagulation monitoring required 1
   • Fewer drug-drug interactions 1
   • No dietary restrictions 1
   • Fixed dosing (5mg twice daily or 2.5mg twice daily for patients with ≥2 of: age ≥80, weight ≤60kg, or serum creatinine ≥1.5mg/dL) 1, 2

2. Practical Benefits:

   • Rapid onset and offset of action 1
   • No need for bridging with parenteral anticoagulants during initiation 1
   • Less need for monitoring visits, improving quality of life 1

Special Populations

Renal Impairment

• For moderate renal impairment (GFR 30-50 ml/min), apixaban is clearly superior to warfarin 1
• For severe renal impairment (GFR <30 ml/min), apixaban may be used with dose adjustment 1
• For end-stage renal disease on dialysis, observational data suggests apixaban may be safer than warfarin, though clinical trial data is limited 1, 4

Cancer Patients

• Apixaban has a predictable pharmacokinetic profile that may be advantageous in cancer patients 1
• Caution needed with potential drug interactions with cancer therapies that affect P-gp or CYP3A4 1

When to Consider Warfarin Instead

Warfarin remains the preferred option in:

• Patients with mechanical heart valves or significant mitral stenosis 1
• Patients who are stable on warfarin with good time in therapeutic range (>65%) and prefer to continue 1
• Patients with severe renal impairment where clinical trial data for apixaban is limited 1
• Cost-sensitive patients without insurance coverage for NOACs 1

Important Considerations and Pitfalls

1. Adherence is Critical:

   • Missing even one dose of apixaban can increase thromboembolism risk due to its shorter half-life 1
   • Warfarin's longer half-life provides some protection during missed doses

2. Reversal Options:

   • Warfarin can be reversed with vitamin K and plasma products
   • Apixaban now has a specific reversal agent (andexanet alfa), though experience is more limited 5

3. Monitoring Challenges:

   • No routine test to measure apixaban's anticoagulant effect in emergency situations 6
   • Warfarin can be monitored with INR

Algorithm for Anticoagulant Selection in Atrial Fibrillation

1. Assess for contraindications to NOACs:

   • Mechanical heart valves or significant mitral stenosis → Use warfarin
   • Severe renal impairment (CrCl <15 ml/min) not on dialysis → Consider warfarin

2. If no contraindications to NOACs:

   • First choice: Apixaban 5mg twice daily (or 2.5mg twice daily if ≥2 of: age ≥80, weight ≤60kg, or serum creatinine ≥1.5mg/dL)
   • Alternative if gastrointestinal bleeding risk is low: Consider other NOACs

3. Consider warfarin if:

   • Patient is stable on warfarin with good TTR (>65%)
   • Cost is prohibitive for NOACs
   • Concerns about adherence to twice-daily dosing
   • Need for frequent monitoring is preferred

In conclusion, for most patients with nonvalvular atrial fibrillation requiring anticoagulation, apixaban offers superior efficacy and safety compared to warfarin, with significant reductions in stroke, bleeding complications, and mortality.