Are Xa (xanthine derivative and factor Xa) inhibitors, such as apixaban (eliquis), appropriate for anticoagulation therapy in patients with atrial fibrillation (a-fib) and heart valve replacement?

Factor Xa Inhibitors for Atrial Fibrillation and Heart Valve Replacement

Recommendation Summary

Factor Xa inhibitors are appropriate for patients with atrial fibrillation, but are NOT recommended for patients with mechanical heart valves. For patients with bioprosthetic valves, apixaban may be considered as an alternative to warfarin. 1

Detailed Recommendations Based on Valve Type

Mechanical Heart Valves

• Warfarin is the ONLY recommended anticoagulant for patients with mechanical heart valves 1
• Direct thrombin inhibitors (dabigatran) are specifically contraindicated for mechanical heart valves 1
• Factor Xa inhibitors (apixaban, rivaroxaban, edoxaban) are not currently recommended for mechanical heart valves due to insufficient evidence 1

Bioprosthetic Heart Valves

• Limited evidence suggests apixaban may be a reasonable alternative to warfarin for patients with AF and bioprosthetic valves 1, 2
• Small subgroups from the ARISTOTLE trial (41 patients with apixaban) and ENGAGE AF-TIMI 48 trial (191 patients with edoxaban) suggest these agents may be equitable alternatives to warfarin in patients with AF and remote bioprosthetic valve implantation 1
• Further study is needed before routine use of Factor Xa inhibitors can be broadly recommended for AF patients with bioprosthetic heart valves 1

Anticoagulation in Non-Valvular Atrial Fibrillation

For patients with non-valvular AF (defined as AF without moderate-to-severe mitral stenosis or mechanical heart valve) and elevated stroke risk:

1. Direct oral anticoagulants (DOACs) are recommended over warfarin (Class I, Level of Evidence: A) 1

   • Options include:
     • Apixaban 5 mg twice daily (standard dose) 1
     • Rivaroxaban 20 mg daily with evening meal 1
     • Edoxaban 60 mg daily 1
     • Dabigatran 150 mg twice daily 1

2. Dose adjustments for apixaban:

   • Reduce to 2.5 mg twice daily if patient has at least 2 of the following: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 3, 4

Special Considerations

Renal Function

• For severe renal impairment or dialysis:
  • Warfarin is preferred for patients with end-stage renal disease (CrCl <15 mL/min) or on dialysis 1
  • Apixaban may be considered at reduced dose (2.5 mg twice daily) for dialysis patients 3
  • Avoid dabigatran, rivaroxaban, and edoxaban in end-stage renal disease 1

Ongoing Research

• The PROACT Xa trial is evaluating apixaban versus warfarin in patients with On-X mechanical aortic valves 5
• Until results from larger trials are available, warfarin remains the standard of care for mechanical valves 6

Common Pitfalls to Avoid

1. Misclassifying valve type: Carefully distinguish between mechanical valves (require warfarin) and bioprosthetic valves (may consider Factor Xa inhibitors) 1

2. Incorrect definition of "non-valvular" AF: This term does not mean absence of any valve disease, but specifically refers to AF without moderate-to-severe mitral stenosis or mechanical heart valve 1

3. Failure to adjust dosing: Factor Xa inhibitors require dose adjustments based on renal function, age, and weight 3, 4

4. Inappropriate discontinuation: Premature discontinuation of any anticoagulant increases thrombotic risk; consider bridging therapy if interruption is necessary 4

By following these evidence-based recommendations, clinicians can optimize anticoagulation therapy for patients with AF and heart valve replacements while minimizing risks of thromboembolism and bleeding.