What is the risk of bleeding vs stroke prevention with apixaban (Apixaban) 10mg twice daily (bid)?

Risk of Bleeding vs Stroke Prevention with Apixaban 10mg BID

Apixaban 10mg twice daily is associated with an excessive bleeding risk that outweighs its stroke prevention benefits and is not recommended for routine use in atrial fibrillation. 1

Bleeding Risk with High-Dose Apixaban

The bleeding risk with apixaban 10mg twice daily is significantly elevated compared to standard dosing:

• In the APPRAISE study, recruitment into the higher dose arms of apixaban (10mg twice daily) was stopped early due to excess bleeding 1
• When apixaban was given at higher doses in acute coronary syndrome patients, there was dose-dependent increase in bleeding 1
• In the APPRAISE-2 trial, even a lower dose of apixaban (5mg twice daily) with dual antiplatelet therapy led to excess bleeding, including intracranial hemorrhage 1

Standard Dosing for Stroke Prevention in Atrial Fibrillation

The evidence supports using lower doses of apixaban for stroke prevention:

• The ARISTOTLE trial demonstrated that apixaban 5mg twice daily (standard dose) was superior to warfarin for stroke prevention with:
  • Lower rates of stroke/systemic embolism (1.27% vs 1.60% per year; HR 0.79) 1, 2
  • Significantly reduced major bleeding (2.13% vs 3.09% per year; HR 0.69) 1, 2
  • Lower rates of hemorrhagic stroke (0.24% vs 0.47%; HR 0.51) 1, 2
  • Reduced all-cause mortality (3.52% vs 3.94%; p=0.047) 1, 2

Risk-Benefit Analysis

When comparing the 10mg BID dose to standard dosing:

• Efficacy: No evidence suggests that 10mg BID provides additional stroke prevention benefit over the standard 5mg BID dose in atrial fibrillation
• Safety: Clear evidence of increased bleeding risk with higher doses 1
• Mortality impact: Higher doses may lead to fatal bleeding events; apixaban at standard doses already shows mortality benefit 3

Special Considerations

For acute VTE treatment, a loading dose of 10mg BID is used only for the first week, followed by 5mg BID thereafter 1. This short-term use of the higher dose has a different risk-benefit profile than long-term use.

Clinical Decision Algorithm

1. For stroke prevention in atrial fibrillation:

   • Use apixaban 5mg BID for most patients
   • Consider dose reduction to 2.5mg BID if patient has ≥2 of: age ≥80 years, weight ≤60kg, or serum creatinine ≥1.5mg/dL 2
   • Avoid 10mg BID dosing due to excessive bleeding risk

2. For acute VTE treatment:

   • 10mg BID is appropriate only for the first 7 days
   • Then reduce to 5mg BID for long-term treatment 1

Common Pitfalls to Avoid

• Using 10mg BID long-term based on perceived higher efficacy - no evidence supports this approach
• Failing to recognize that bleeding risk increases in a dose-dependent manner with apixaban 1
• Overlooking that even the 5mg BID dose showed increased bleeding when combined with dual antiplatelet therapy 1

The evidence clearly demonstrates that the standard apixaban dosing regimen (5mg BID with appropriate dose reductions for high-risk patients) provides the optimal balance between stroke prevention and bleeding risk.