What is the failure rate of Eliquis (apixaban) in preventing stroke and systemic embolism in patients with non-valvular atrial fibrillation?

Eliquis (Apixaban) Failure Rate in Preventing Stroke in Non-valvular Atrial Fibrillation

Eliquis (apixaban) has a failure rate of approximately 1.27% per year for stroke or systemic embolism in patients with non-valvular atrial fibrillation, which represents a 21% reduction in events compared to warfarin. 1, 2

Efficacy Data from Major Clinical Trials

ARISTOTLE Trial Results

The ARISTOTLE trial provides the most comprehensive data on apixaban's efficacy:

• Primary outcome (stroke or systemic embolism):

  • Apixaban: 1.27% per year
  • Warfarin: 1.60% per year
  • Hazard Ratio: 0.79 (95% CI: 0.66-0.95, p=0.01 for superiority) 1, 2

• Breakdown of stroke types:

  • Ischemic stroke without hemorrhage: 0.83% per year (apixaban) vs 0.82% per year (warfarin)
  • Hemorrhagic stroke: 0.24% per year (apixaban) vs 0.47% per year (warfarin) 1
  • Ischemic stroke with hemorrhagic conversion: 0.07% per year (apixaban) vs 0.12% per year (warfarin) 2

AVERROES Trial Results

For patients unsuitable for warfarin therapy, the AVERROES trial compared apixaban to aspirin:

• Primary outcome (stroke or systemic embolism):
  • Apixaban: 1.6% per year
  • Aspirin: 3.7% per year
  • Hazard Ratio: 0.45 (95% CI: 0.32-0.62) 1

Safety Profile

Apixaban demonstrates a superior safety profile compared to warfarin:

• Major bleeding:

  • Apixaban: 2.13% per year
  • Warfarin: 3.09% per year
  • Hazard Ratio: 0.69 (95% CI: 0.60-0.80) 1, 3

• Intracranial hemorrhage:

  • Apixaban: 0.24% per year
  • Warfarin: 0.47% per year
  • 49% reduction compared to warfarin 3, 2

Consistency Across Patient Subgroups

The efficacy of apixaban is consistent across various patient subgroups:

• Primary prevention (patients without prior stroke/TIA):

  • 1.01% per year (apixaban) vs 1.23% per year (warfarin)
  • Hazard Ratio: 0.82 (95% CI: 0.65-1.03) 1

• Renal impairment:

  • Consistent efficacy in patients with impaired renal function
  • Greater reduction in major bleeding among those with advanced dysfunction (eGFR ≤50 mL/min) 1

• Other factors:

  • Consistent benefits across age, weight, CHADS₂ score, prior warfarin use, and geographic region 2

Important Clinical Considerations

Dosing

• Standard dose: 5 mg twice daily
• Reduced dose (2.5 mg twice daily) for patients with at least 2 of:
  • Age ≥80 years
  • Body weight ≤60 kg
  • Serum creatinine ≥1.5 mg/dL 3, 2

Potential Pitfalls

1. Discontinuation risk: Clustering of stroke events has been observed after discontinuation of apixaban. Coverage with another anticoagulant should be strongly considered when stopping apixaban unless there is pathological bleeding 1

2. Dosing errors: Studies show that approximately 12-17% of hospitalized patients may receive incorrect dosing, most commonly underdosing in elderly patients 4

3. Renal function: Regular monitoring of renal function is essential, as dosing adjustments are needed for patients with severe renal impairment 3

4. Drug interactions: Strong inhibitors of CYP3A4 and P-glycoprotein can increase apixaban levels and bleeding risk 3

Meta-analysis Evidence

A 2022 meta-analysis of nine studies with 267,998 patients confirmed that apixaban was associated with:

• Significant decrease in stroke or systemic embolism (RR: 0.77,95% CI: 0.67-0.90)
• Significant reduction in major bleeding events (RR: 0.63,95% CI: 0.58-0.68) compared to warfarin 5

In conclusion, Eliquis (apixaban) has a failure rate of 1.27% per year for preventing stroke or systemic embolism in patients with non-valvular atrial fibrillation, representing a 21% improvement over warfarin with a significantly better safety profile, particularly regarding intracranial hemorrhage.