Is Apixaban Contraindicated in Patients with Valve Replacement?
Apixaban is absolutely contraindicated in patients with mechanical heart valves, but may be used cautiously in select patients with bioprosthetic valves who have atrial fibrillation and are at least 3 months post-implantation. 1
Mechanical Heart Valves: Absolute Contraindication
Direct oral anticoagulants including apixaban should not be used in patients with mechanical valve prostheses (Class III: Harm recommendation). 1 This is based on:
The RE-ALIGN trial was stopped prematurely due to excessive thrombotic complications when dabigatran (another direct oral anticoagulant) was compared to warfarin in mechanical valve patients. Stroke occurred in 5% of dabigatran patients versus 0% in warfarin patients, and major bleeding was also significantly higher (4% vs 2%). 1
The FDA has issued a specific contraindication for direct thrombin inhibitors and anti-Xa agents (including apixaban) in patients with mechanical heart valves. 1
The 2023 PROACT Xa trial confirmed these findings specifically for apixaban in patients with On-X mechanical aortic valves. The trial was stopped early after enrolling 863 patients due to excess thromboembolic events in the apixaban group (4.2%/patient-year) compared to warfarin (1.3%/patient-year), failing to meet noninferiority criteria. 2
Warfarin remains the only approved oral anticoagulant for mechanical heart valves with target INR 2.0-3.0. 1
Bioprosthetic Heart Valves: Conditional Use
The situation differs substantially for bioprosthetic valves:
When Apixaban May Be Considered:
Patients with atrial fibrillation and bioprosthetic valves (at least 3 months post-implantation) may use apixaban based on subgroup analyses from the ARISTOTLE trial, which included 104 patients with bioprosthetic valves. 1, 3
The 2019 AHA/ACC/HRS guidelines note that small numbers of patients with mitral or aortic bioprosthetic valve implants were included in the ARISTOTLE (41 patients) and ENGAGE AF-TIMI 48 (191 patients) trials, suggesting apixaban and edoxaban appeared to be equitable alternatives to warfarin in patients with remote bioprosthetic valve implantation. 1
Retrospective data from 54 patients who received apixaban following bioprosthetic valve replacement showed it was safe and well-tolerated, with major bleeding in only 2% and thrombotic events in 2% of patients. 4
Critical Caveats for Bioprosthetic Valves:
These agents are not recommended due to lack of data on their safety and effectiveness in patients with bioprosthetic valves who require anticoagulation, according to the 2014 AHA/ACC guidelines. 1
The CHA₂DS₂-VASc scoring system has not been validated for long-term assessment of thromboembolism risk in patients with bioprosthetic valves and AF, though one study suggested low scores were associated with low risk regardless of bioprosthetic valve presence. 1
Short-term anticoagulation (3-6 months) after bioprosthetic valve implantation typically uses warfarin with INR target 2.0-3.0, not DOACs. 1
Special Populations
Rheumatic Heart Disease with Moderate-to-Severe Mitral Stenosis:
DOACs including apixaban are specifically contraindicated in patients with moderate-to-severe mitral stenosis, which is common in rheumatic heart disease. 5, 6 These patients require warfarin. 5
TAVR (Transcatheter Aortic Valve Replacement):
Bioprosthetic valves implanted via TAVR have not been adequately studied with apixaban. The standard post-TAVR regimen is dual antiplatelet therapy (aspirin plus clopidogrel) for 6 months, not DOACs. 1
FDA Labeling Position
The FDA drug label for apixaban explicitly states: "The safety and efficacy of apixaban tablets have not been studied in patients with prosthetic heart valves. Therefore, use of apixaban tablets is not recommended in these patients." 7
Clinical Algorithm
For mechanical valves: Use warfarin only (INR 2.0-3.0). Apixaban is contraindicated. 1, 2
For bioprosthetic valves:
- If <3 months post-implantation: Use warfarin (INR 2.0-3.0). 1
- If ≥3 months post-implantation AND patient has atrial fibrillation: Apixaban may be considered as an alternative to warfarin, though warfarin remains preferred due to limited data. 1, 3
- If ≥3 months post-implantation AND no atrial fibrillation: Typically no anticoagulation needed; use antiplatelet therapy only. 1
For moderate-to-severe mitral stenosis (including rheumatic): Use warfarin only. Apixaban is contraindicated. 5, 6