Is Eliquis (apixaban) contraindicated in rheumatic mitral valve disease?

Is Eliquis Contraindicated in Rheumatic Mitral Valve Disease?

Yes, Eliquis (apixaban) is absolutely contraindicated in patients with moderate-to-severe rheumatic mitral stenosis, and warfarin is the only acceptable anticoagulant for this condition.

Absolute Contraindication for NOACs

• Direct oral anticoagulants (NOACs), including apixaban, are contraindicated in patients with moderate-to-severe mitral stenosis or mechanical heart valves. 1
• The 2019 AHA/ACC/HRS guidelines explicitly state that NOACs are recommended over warfarin in NOAC-eligible patients with atrial fibrillation "except with moderate-to-severe mitral stenosis or a mechanical heart valve." 1
• This contraindication applies to all NOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) and represents a Class 3: Harm recommendation. 2

Why Warfarin Is Mandatory

• Warfarin with a target INR of 2.5 (range 2.0-3.0) is the only recommended anticoagulant for rheumatic mitral valve disease. 2, 3
• Rheumatic mitral stenosis increases stroke risk 20-fold compared to patients in sinus rhythm, making effective anticoagulation critical. 2
• All patients with rheumatic mitral stenosis and atrial fibrillation require warfarin anticoagulation, regardless of stenosis severity. 2
• Even patients in sinus rhythm should receive warfarin when high-risk features are present, such as left atrial diameter ≥55 mm, history of systemic thromboembolism, or left atrial thrombus. 2

Evidence Base for the Contraindication

• All pivotal NOAC trials explicitly excluded patients with moderate-to-severe mitral stenosis, meaning there is no safety or efficacy data for apixaban in this population. 3, 4
• The ARISTOTLE trial, which established apixaban's efficacy, only excluded patients with "clinically significant mitral stenosis," and the 26.4% of patients with valvular heart disease in that trial did not include those with rheumatic mitral stenosis. 5
• The restrictive definition of "valvular AF" that contraindicates NOACs specifically refers to rheumatic mitral stenosis and mechanical prosthetic valves. 4

Clinical Algorithm for Anticoagulation Decision

For patients with rheumatic mitral valve disease:

1. If atrial fibrillation is present: Warfarin is absolutely mandatory (INR 2.0-3.0). 2, 3
2. If sinus rhythm with high-risk features: Warfarin strongly recommended (INR 2.0-3.0). 2
   • High-risk features include: left atrial diameter ≥55 mm, history of thromboembolism, left atrial thrombus, or dense spontaneous echo contrast. 2
3. Never use apixaban or any other NOAC in moderate-to-severe rheumatic mitral stenosis. 1, 2, 3

Monitoring Requirements

• INR should be checked weekly during warfarin initiation and monthly once stable in therapeutic range. 1, 6, 3
• Renal and hepatic function should be reassessed at least annually. 1
• Strive for the highest possible time in therapeutic range (TTR) to maximize efficacy and minimize complications. 3

Critical Pitfall to Avoid

Do not confuse rheumatic mitral stenosis with other forms of valvular disease. Patients with bioprosthetic valves (beyond 3 months post-implantation), mild mitral regurgitation, or aortic valve disease without mitral stenosis may be eligible for NOACs. 3 However, if the underlying pathology is rheumatic mitral stenosis—even after bioprosthetic valve replacement—warfarin remains mandatory because the rheumatic disease maintains high thromboembolic risk. 3