Is Apixaban Cleared for Use in Valvular AF?
Apixaban is NOT cleared for use in true valvular AF, which is specifically defined as AF with moderate-to-severe mitral stenosis or mechanical heart valves—these are absolute contraindications requiring warfarin instead. 1, 2
However, the term "valvular AF" is misleading in modern practice, as apixaban IS approved for most other forms of valvular heart disease that were historically grouped under this label.
Understanding the Critical Definition
The 2019 AHA/ACC/HRS guidelines fundamentally redefined valvular AF to clarify this confusion 1:
- True "valvular AF" (apixaban contraindicated): Only moderate-to-severe mitral stenosis OR mechanical heart valves 1, 2
- "Nonvalvular AF" (apixaban approved): All other scenarios, including patients with mild mitral stenosis, mitral regurgitation, aortic stenosis, aortic regurgitation, tricuspid regurgitation, bioprosthetic valves, valve repair, and valvuloplasty 1, 3
This distinction matters because approximately 20% of patients in major NOAC trials had various valvular defects, yet these patients are now classified as having "nonvalvular AF" for treatment purposes 1.
Absolute Contraindications for Apixaban
Mechanical heart valves:
- Apixaban must never be used in patients with mechanical prosthetic valves due to excessive thrombotic complications and increased major bleeding risk 3
- Warfarin remains the only approved anticoagulant for this population 1, 4
Moderate-to-severe mitral stenosis:
- Apixaban is contraindicated; warfarin with target INR 2.0-3.0 is required 3
- This is particularly common in rheumatic heart disease 3
When Apixaban CAN Be Used in Valvular Heart Disease
Bioprosthetic valves:
- Apixaban is appropriate for patients with bioprosthetic valves at least 3 months post-implantation 3, 5
- The ARISTOTLE trial subanalysis (n=104 with bioprosthetic valves) showed consistent safety and efficacy compared to warfarin, though event rates were low 5
Other valvular lesions:
- Apixaban is recommended over warfarin for AF patients with aortic stenosis, aortic regurgitation, mitral regurgitation, tricuspid regurgitation, and mild mitral stenosis 3, 4
- The ARISTOTLE trial demonstrated that apixaban maintained superiority over warfarin in patients with mitral regurgitation (HR 0.69,95% CI 0.46-1.04), aortic regurgitation (HR 0.57,95% CI 0.27-1.20), and aortic stenosis (HR 0.44,95% CI 0.17-1.13), with no evidence of different treatment effects 6
Valve repair:
- Patients with prior valve repair or valvuloplasty can receive apixaban 1, 3, 5
- ARISTOTLE included 52 patients with valve repair (50 mitral, 2 aortic) with consistent results 5
Clinical Decision Algorithm
Step 1: Identify valve pathology type 3
- If mechanical valve → Use warfarin only 1, 3
- If moderate-to-severe mitral stenosis → Use warfarin only 1, 3
- If other valvular disease → Proceed to Step 2
Step 2: Assess timing for bioprosthetic valves 3
- If <3 months post-implantation → Use warfarin
- If ≥3 months post-implantation → Apixaban is appropriate
Step 3: Calculate CHA₂DS₂-VASc score 3
- Score ≥2 in men or ≥3 in women → Anticoagulation indicated 1
Step 4: Check renal function for dosing 3, 4
- Standard dose: 5 mg twice daily 3
- Reduced dose (2.5 mg twice daily): If ≥2 of the following: age ≥80 years, weight ≤60 kg, creatinine ≥1.5 mg/dL 3
- End-stage renal disease (CrCl <15 mL/min): Warfarin preferred, though apixaban may be reasonable 4
Important Caveats
Aortic stenosis carries higher baseline risk:
- Patients with aortic stenosis had significantly higher rates of stroke/systemic embolism (3.47 vs 1.36 per 100 patient-years), death (8.30 vs 3.53), and major bleeding (5.31 vs 2.53) compared to those without aortic stenosis, though apixaban remained superior to warfarin 6
FDA labeling specificity:
- The FDA label for apixaban explicitly states indication for "nonvalvular atrial fibrillation" without defining the term 2
- Clinical practice must rely on guideline definitions rather than FDA labeling alone 1
Real-world dosing errors: