Warfarin for Secondary Stroke Prevention in Rheumatic Mitral Stenosis with Atrial Fibrillation
In a patient with severe rheumatic mitral valve stenosis and atrial fibrillation who has already had a stroke, warfarin with a target INR of 2.0-3.0 is the only recommended anticoagulant for secondary stroke prevention. 1, 2
Why Warfarin is Mandatory
Direct oral anticoagulants (DOACs) like apixaban are absolutely contraindicated in moderate to severe mitral stenosis. 1 The 2021 AHA/ASA Stroke Prevention Guidelines explicitly state that DOACs should NOT be used in patients with moderate to severe mitral stenosis or mechanical heart valves, giving this a Class 3: Harm recommendation. 1, 2 This is critical because:
- All major DOAC trials (RE-LY, ROCKET-AF, ARISTOTLE, ENGAGE AF-TIMI 48) specifically excluded patients with moderate to severe mitral stenosis 1, 3
- No randomized controlled trial has validated DOAC safety or efficacy in rheumatic valve disease 4
- The pathophysiology of rheumatic mitral stenosis creates unique thrombogenic conditions in the left atrium that differ from nonvalvular AF 2, 5
Why Aspirin is Inadequate
Aspirin alone provides insufficient stroke protection in this high-risk population. 4, 6 The evidence is clear:
- Aspirin reduces stroke risk by only 19-22% compared to placebo in atrial fibrillation 4
- Warfarin reduces stroke risk by 62-64% in the same population 4
- A prospective randomized trial in patients with rheumatic mitral valve disease and AF showed significantly more embolic events with aspirin (15 events) compared to warfarin with adequate INR control (3 events), p < 0.0061 6
- Current guidelines explicitly advise against antiplatelet therapy when oral anticoagulation is indicated for AF with valvular disease 1, 4
Warfarin Dosing and Monitoring Protocol
Target INR: 2.5 (range 2.0-3.0) 1, 2, 7
Initiation Strategy:
- Start with 2-5 mg daily (avoid loading doses which increase hemorrhagic complications) 2, 7
- Check INR weekly during the first weeks of therapy 1, 2, 7
- Once stable in therapeutic range, check INR monthly 1, 2, 7
Critical Monitoring Requirements:
- Reassess renal and hepatic function at least annually 2
- If time in therapeutic range (TTR) is <65-70%, intensify monitoring and patient education rather than switching medications 4
- When INR is subtherapeutic (<2.0), stroke risk increases dramatically—in one study, 21 of 24 embolic events in the warfarin group occurred with INR <2.0 6
Common Pitfalls to Avoid
Never substitute a DOAC for warfarin in this population, even if INR control is difficult—this is a contraindication, not a relative concern 1, 2, 4
Do not use aspirin as monotherapy—the stroke risk in rheumatic mitral stenosis with AF is 4% per year, and aspirin provides inadequate protection 4, 6, 5
Do not add aspirin to warfarin in this setting unless the patient also has a mechanical mitral valve (which would require INR 2.5-3.5 plus aspirin 75-100 mg daily) 1, 7
Recognize that this is "valvular AF"—the presence of moderate to severe mitral stenosis automatically classifies this as valvular AF, which mandates warfarin therapy regardless of CHA₂DS₂-VASc score 1, 2, 4
Special Considerations for Secondary Prevention
Since this patient has already had a stroke, they are at extremely high risk for recurrence. 2 The 2023 World Stroke Organization guidelines specifically state that oral anticoagulation is recommended for patients with ischemic stroke or TIA and valvular atrial fibrillation (defined as mechanical valve replacement or moderate/severe mitral stenosis). 1 The AHA/ASA guidelines emphasize that warfarin is mandatory regardless of whether atrial fibrillation is present, though AF further increases the indication strength. 2
The combination of rheumatic mitral stenosis + atrial fibrillation + prior stroke creates a 20-fold increased stroke risk compared to patients in sinus rhythm, making meticulous anticoagulation with warfarin absolutely essential. 2