What are the recommendations for using novel anticoagulants, such as apixaban (Apixaban) and rivaroxaban (Rivaroxaban), in patients with atrial fibrillation or deep vein thrombosis/pulmonary embolism?

Recommendations for Novel Anticoagulants in Atrial Fibrillation and VTE

Direct oral anticoagulants (DOACs) such as apixaban and rivaroxaban are strongly recommended over vitamin K antagonists (VKAs) for stroke prevention in non-valvular atrial fibrillation and for treatment of deep vein thrombosis/pulmonary embolism due to their superior safety profile and comparable efficacy.

General Recommendations for DOACs

Atrial Fibrillation

• DOACs are preferred over VKAs (warfarin) for stroke prevention in non-valvular atrial fibrillation due to:

  • 19% reduction in stroke or systemic embolism
  • 51% reduction in hemorrhagic stroke
  • 10% reduction in overall mortality
  • 52% reduction in intracranial bleeding 1, 2

• Contraindications for DOACs in AF:

  • Mechanical heart valves
  • Moderate-to-severe mitral stenosis
  • Severe renal failure (specific thresholds vary by agent)
  • Active major bleeding 1, 2

Venous Thromboembolism (DVT/PE)

• DOACs are recommended for treatment of VTE and prevention of recurrence 1
• Initial treatment dosing differs from maintenance dosing (see specific dosing below)
• For cancer-associated VTE, low-molecular-weight heparin or a DOAC is recommended rather than a VKA 1

Specific DOAC Recommendations

Apixaban (Eliquis)

• AF dosing: 5 mg twice daily
  • Reduce to 2.5 mg twice daily if patient has at least 2 of: age ≥80 years, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 1, 3
• VTE treatment dosing: 10 mg twice daily for 7 days, then 5 mg twice daily 1, 3
• VTE secondary prevention: 2.5 mg twice daily after at least 6 months of treatment 1, 3
• Benefits: Lowest bleeding risk among DOACs, can be used in severe renal impairment (CrCl 15-29 mL/min) 2, 4

Rivaroxaban (Xarelto)

• AF dosing: 20 mg once daily with food
  • Reduce to 15 mg once daily if CrCl 15-49 mL/min 1
• VTE treatment dosing: 15 mg twice daily with food for first 21 days, then 20 mg once daily with food 1
• VTE secondary prevention: 10 mg once daily after 6 months of initial therapy 1
• Note: Must be taken with food for optimal absorption in AF and VTE treatment 1

Comparative Effectiveness and Safety

Recent evidence shows that apixaban may have a more favorable safety profile compared to rivaroxaban:

• A large retrospective cohort study of Medicare beneficiaries found that rivaroxaban was associated with significantly higher risk of major ischemic or hemorrhagic events compared to apixaban (HR 1.18,95% CI 1.12-1.24) 4
• Apixaban demonstrated a 31% reduction in major bleeding compared to warfarin, which appears to be better than other DOACs 2

Perioperative Management

• Discontinue apixaban 48 hours before elective surgery with significant bleeding risk 1, 2
• Discontinue rivaroxaban 48 hours before elective surgery with significant bleeding risk 1
• Resume DOACs as soon as adequate hemostasis is achieved, typically 24-72 hours postoperatively 1
• No bridging with heparin is typically required when stopping DOACs for procedures 1

Special Populations

Renal Impairment

• Severe renal impairment (CrCl 15-29 mL/min):
  • Apixaban: 2.5 mg twice daily
  • Rivaroxaban: 15 mg once daily
  • Both require careful monitoring 1, 3

End-Stage Renal Disease/Dialysis

• Apixaban is the only DOAC specifically mentioned in guidelines for use in dialysis patients 2
• Standard dosing adjustments apply based on age, weight, and creatinine 2

Monitoring and Follow-up

• Regular monitoring of renal function is essential
• No routine coagulation monitoring is required
• Monitor for drug interactions, particularly with strong inhibitors of CYP3A4 and P-glycoprotein 2
• Assess for bleeding signs at each follow-up visit

Common Pitfalls to Avoid

1. Inappropriate dose reduction: Using reduced doses without meeting criteria leads to increased thrombotic risk 1
2. Failure to adjust for renal function: Renal function should be assessed before starting therapy and periodically thereafter
3. Drug interactions: Be vigilant about interactions with P-glycoprotein inhibitors and CYP3A4 inhibitors
4. Abrupt discontinuation: Stopping DOACs without appropriate bridging or transition increases thrombotic risk 3
5. Incorrect dosing for indication: VTE treatment requires different dosing than AF prevention, particularly during initiation 1

In conclusion, DOACs offer significant advantages over traditional VKAs for both AF and VTE, with apixaban showing the most favorable safety profile among the available options. Selection should be based on patient characteristics, particularly renal function, concomitant medications, and bleeding risk.