Eliquis (Apixaban) Should NOT Be Used in Moderate Mitral Stenosis
Apixaban is contraindicated in patients with moderate to severe mitral stenosis, regardless of whether atrial fibrillation is present—warfarin is the only recommended anticoagulant for this condition. 1, 2
Why Apixaban is Contraindicated
The 2021 AHA/ASA Stroke Prevention Guidelines explicitly define "valvular atrial fibrillation" as AF occurring with moderate to severe mitral stenosis or mechanical heart valves, and state that direct oral anticoagulants (DOACs) including apixaban are not recommended in these patients. 1
- The European Society of Cardiology mandates vitamin K antagonist (warfarin) with target INR 2.0-3.0 for all patients with moderate to severe rheumatic mitral stenosis and atrial fibrillation. 2
- DOACs are explicitly contraindicated in moderate to severe mitral stenosis because all major DOAC trials systematically excluded these patients. 2, 3
- The ARISTOTLE trial, which established apixaban's efficacy, specifically excluded patients with "clinically significant mitral stenosis." 4
The Correct Anticoagulation Strategy
For Patients WITH Atrial Fibrillation:
- Warfarin with target INR 2.5 (range 2.0-3.0) is mandatory, regardless of stenosis severity. 2
- Start warfarin at 2-5 mg daily, avoiding loading doses to minimize hemorrhagic complications. 2
- Check INR weekly during initiation, then monthly once stable in therapeutic range. 2
For Patients in Sinus Rhythm:
- Warfarin (INR 2.0-3.0) is strongly recommended when high-risk features are present: 2
- History of systemic thromboembolism
- Left atrial thrombus on echocardiography
- Left atrial diameter ≥55 mm
- Dense spontaneous echo contrast in the left atrium
Why This Restriction Exists
The pathophysiology of mitral stenosis creates unique thrombotic risks that differ fundamentally from other valvular conditions:
- Chronic atrial pressure elevation, inflammation, and fibrosis create a prothrombotic milieu that may not respond to DOACs the same way as typical AF. 3
- The annual stroke risk in mitral stenosis with AF is approximately 4% per year—substantially higher than typical AF. 3
- Even after valve replacement, specific atrial changes from mitral stenosis may persist and influence thromboembolic events differently with DOACs versus warfarin. 3
Emerging Research (Not Yet Guideline-Supported)
While some observational data suggest potential DOAC efficacy, these findings are not sufficient to change current practice:
- A 2019 Korean registry study (n=2,230) showed lower thromboembolism rates with DOACs versus warfarin in mitral stenosis patients (2.22% vs 4.19%/year), but this was observational and hypothesis-generating only. 5
- The ongoing DAVID-MS trial is comparing dabigatran to warfarin in moderate-severe mitral stenosis, but results are not yet available. 3
- Until randomized controlled trial data specifically in mitral stenosis patients demonstrate safety and efficacy, warfarin remains the only evidence-based choice. 2, 3
Critical Pitfall to Avoid
Do not confuse "nonvalvular AF" with "absence of valve disease." The term "nonvalvular AF" specifically means AF without moderate-severe mitral stenosis or mechanical valves—patients can have other valve diseases (mild mitral stenosis, mitral regurgitation, aortic stenosis, mitral valve prolapse) and still be candidates for DOACs. 1 However, moderate mitral stenosis crosses this threshold and mandates warfarin therapy.