What is the recommended approach for initiating warfarin (International Normalized Ratio (INR) anticoagulant) therapy in patients with severe aortic stenosis?

Warfarin Initiation in Severe Aortic Stenosis

Warfarin can be safely initiated in patients with severe aortic stenosis when anticoagulation is indicated (such as for atrial fibrillation), using standard dosing protocols with a target INR of 2.0-3.0, though these patients require careful monitoring due to increased bleeding risk. 1, 2

Clinical Context and Indications

Severe aortic stenosis itself is not an indication for anticoagulation. 3 Warfarin should only be initiated when there is a separate indication such as:

• Atrial fibrillation with elevated CHA₂DS₂-VASc score (≥2 in men, ≥3 in women) 3
• Mechanical heart valve replacement (if the patient undergoes valve replacement) 3
• Mitral stenosis with atrial fibrillation or other high-risk features 1
• Documented left atrial thrombus or prior systemic embolism 3

Important caveat: Direct oral anticoagulants (DOACs) are contraindicated in moderate-to-severe mitral stenosis but are not contraindicated in aortic stenosis. 3 However, recent observational data suggest warfarin may be superior to DOACs in patients with both atrial fibrillation and aortic stenosis, showing lower thromboembolism rates despite higher bleeding risk. 4, 5

Initial Dosing Protocol

Start with 2-5 mg daily; avoid loading doses. 2 The lower end of this range (2-3 mg) is preferred for:

• Elderly patients (≥75 years) 3
• Patients with potential for enhanced warfarin sensitivity 2
• Those with multiple comorbidities 3

Do not use loading doses (e.g., 10 mg), as this increases hemorrhagic complications without providing faster therapeutic protection. 2

INR Monitoring Schedule

Initiation Phase:

• Check INR daily until therapeutic range (2.0-3.0) is reached and sustained for 2 consecutive days 6
• Then check 2-3 times weekly for 1-2 weeks 6
• Then check weekly for approximately 1 month 6

Maintenance Phase:

• Check INR at least monthly once stable in therapeutic range 3, 6
• May extend to every 12 weeks if consistently stable, though monthly is safer in aortic stenosis patients given their higher bleeding risk 6, 5

Triggers for More Frequent Monitoring:

• Any medication changes (especially antibiotics, antiarrhythmics, NSAIDs) 6
• Dietary changes or weight fluctuations 6
• Intercurrent illness 6
• Any bleeding episode or INR fluctuation 6

Target INR Range

Standard target: INR 2.5 (range 2.0-3.0) for most indications in aortic stenosis patients. 2

Specific scenarios:

• Atrial fibrillation alone: INR 2.0-3.0 3, 2
• Bileaflet mechanical aortic valve (if replaced): INR 2.0-3.0 3, 2
• Mechanical mitral valve or older valve types: INR 2.5-3.5 2
• History of thromboembolism despite therapeutic INR: Consider higher range (2.5-3.5) and add aspirin 75-100 mg daily 7

Special Considerations for Aortic Stenosis

Bleeding risk is substantially elevated in patients with aortic stenosis and atrial fibrillation compared to those without valvular disease. 5 Specifically:

• Gastrointestinal bleeding risk is 63% higher (adjusted HR 1.63) 5
• Overall bleeding risk is 36% higher (adjusted HR 1.36) 5
• This elevated risk persists even with careful INR control 5

Thromboembolism considerations:

• Aortic stenosis patients on warfarin have lower stroke rates than those on DOACs (contrary to most AF populations) 4
• Annual cholesterol embolization risk with therapeutic warfarin is low (0.7%) despite aortic plaque burden 8

Common Pitfalls to Avoid

Do not use DOACs reflexively in aortic stenosis with atrial fibrillation—while not contraindicated, emerging evidence suggests warfarin may be superior for stroke prevention in this specific population. 4, 5

Do not extend monitoring intervals prematurely—patients with aortic stenosis require more vigilant monitoring due to their elevated bleeding risk. 6, 5

Do not ignore genetic factors—CYP2C9*2 and *3 variants are associated with lower time in therapeutic range and require dose adjustments in valve patients. 9

Do not assume standard INR ranges are adequate for all patients—those with recurrent thromboembolism despite therapeutic INR may require higher targets (2.5-3.5) plus aspirin. 7

Do not forget aspirin consideration—for mechanical valves or recurrent thromboembolism, add low-dose aspirin (75-100 mg daily) to warfarin. 3, 2, 7

Reassessment Strategy

Reevaluate anticoagulation need and choice at periodic intervals to reassess stroke and bleeding risks, particularly if the patient undergoes valve replacement or develops new comorbidities. 3