What anticoagulant is recommended for a patient with Rheumatic Heart Disease (RHD) and mitral stenosis who has experienced a stroke?

Warfarin Anticoagulation for RHD with Mitral Stenosis and Stroke

For patients with rheumatic heart disease (RHD) and mitral stenosis who have experienced a stroke, warfarin anticoagulation with a target INR of 2.5 (range 2.0-3.0) is the recommended treatment, regardless of whether atrial fibrillation is present. 1, 2

Primary Anticoagulation Strategy

Long-term warfarin therapy is the cornerstone of stroke prevention in this population. The American Heart Association/American Stroke Association provides a Class IIa recommendation (Level of Evidence C) for warfarin with target INR 2.5 (range 2.0-3.0) in patients with rheumatic mitral valve disease who have experienced ischemic stroke or TIA. 1

Key Evidence Supporting Warfarin

• Recurrent embolism occurs in 30-65% of patients with rheumatic mitral valve disease who have a history of previous embolic events, with 60-65% of recurrences developing within the first year (most within 6 months). 1
• Multiple observational studies demonstrate that long-term anticoagulant therapy effectively reduces the risk of systemic embolism in patients with rheumatic mitral valve disease. 1
• The presence of previous systemic embolism (stroke) is itself an absolute indication for anticoagulation in rheumatic mitral valve disease, independent of whether a clot is currently visible on imaging. 2

Target INR and Monitoring

Maintain INR at 2.5 with therapeutic range of 2.0-3.0. 1, 2, 3

Monitoring Protocol

• Check INR weekly during warfarin initiation, then reduce to monthly once stable in therapeutic range. 4
• Aim for time in therapeutic range (TTR) >65% to minimize both thromboembolism and bleeding complications. 2, 3
• Start warfarin at 2-5 mg daily, avoiding loading doses to minimize hemorrhagic complications. 4, 5
• Reassess renal and hepatic function at least annually. 4

INR Targets to Remember

• Standard target for native rheumatic valve disease: INR 2.5 (range 2.0-3.0) 1, 2, 3
• Higher INR target (2.5-3.5) is reserved only for mechanical prosthetic valves, not native valve disease. 2, 5
• Subtherapeutic anticoagulation (INR <2.0) significantly increases thromboembolism risk. 3
• INR values >3.0 increase major bleeding risk, especially intracranial hemorrhage when INR rises above 3.5. 3

Management of Recurrent Stroke on Warfarin

If the patient experiences another ischemic stroke while on therapeutic warfarin (INR 2.0-3.0), add aspirin 81 mg daily. The American Heart Association provides a Class IIa recommendation (Level of Evidence C) for adding low-dose aspirin in patients with rheumatic mitral valve disease who have recurrent embolism despite warfarin therapy. 1, 2

Important Caveat

• Do not routinely add antiplatelet agents to warfarin initially (Class III recommendation), as combination therapy increases bleeding risk without proven benefit in the absence of recurrent events. 1, 2

Why NOT Direct Oral Anticoagulants (DOACs)

DOACs are absolutely contraindicated in moderate to severe mitral stenosis. 2, 4

Evidence Against DOACs

• The 2021 AHA/ASA guidelines explicitly state that DOACs should not be used in patients with moderate to severe mitral stenosis or mechanical heart valves (Class 3: Harm recommendation). 2, 4
• The INVICTUS trial (2023) demonstrated that VKA-treated patients with moderate to severe rheumatic mitral stenosis and AF exhibited lower event rates (including mortality) compared to rivaroxaban. 6
• All major DOAC trials excluded patients with rheumatic heart disease and moderate to severe mitral stenosis. 2, 7
• While one observational Korean study suggested potential benefit of DOACs in mitral stenosis, this contradicts the randomized INVICTUS trial and remains hypothesis-generating only. 8

Clinical Algorithm for Implementation

Step 1: Initiate Warfarin

• Start warfarin 2-5 mg daily (lower dose for elderly or debilitated patients). 4, 5
• Check baseline INR, CBC, renal and hepatic function. 4

Step 2: Dose Adjustment Phase

• Check INR every 2-3 days initially, then weekly until stable. 4
• Adjust dose based on INR results to achieve target 2.0-3.0. 5

Step 3: Maintenance Phase

• Once stable, check INR monthly. 4
• Most patients maintained on 2-10 mg daily. 5
• Ensure TTR >65%. 2, 3

Step 4: If Recurrent Stroke Occurs on Therapeutic Warfarin

• Verify INR was therapeutic at time of event. 2
• Add aspirin 81 mg daily. 1, 2
• Continue warfarin at same target INR 2.0-3.0. 2

Critical Pitfalls to Avoid

Do NOT delay anticoagulation waiting for clot resolution on imaging

The absence of visible thrombus does not negate the indication for anticoagulation when previous systemic embolism has occurred. 2

Do NOT use antiplatelet monotherapy

Aspirin or clopidogrel alone is insufficient for stroke prevention in rheumatic mitral stenosis with prior stroke. Observational studies demonstrate that anticoagulation is far superior to antiplatelet therapy in reducing recurrent embolism. 2, 4

Do NOT target INR >3.0 in native valve disease

The higher INR target (2.5-3.5) is only for mechanical prosthetic valves, not native rheumatic valve disease. 2, 5

Do NOT use DOACs

Despite off-label use in some settings, DOACs remain contraindicated based on the INVICTUS trial results and guideline recommendations. 2, 4, 6

Do NOT assume successful valvuloplasty eliminates anticoagulation need

Mitral valvuloplasty does not eliminate the risk of thromboembolism; successful valvuloplasty does not eliminate the need for anticoagulation in patients requiring long-term anticoagulation preoperatively. 1

Special Considerations

Dietary and Drug Interactions

• Maintain consistent vitamin K intake through diet to avoid INR fluctuations. 3
• Drug interactions can significantly alter warfarin metabolism, requiring more frequent monitoring when starting or stopping medications. 3

Bridging Therapy

• For high-risk perioperative scenarios, use enoxaparin 1 mg/kg subcutaneously every 12 hours when INR falls below 2.0. 4
• Reduce to 0.75 mg/kg every 12 hours for elderly patients ≥75 years. 4
• For severe renal impairment (CrCl <30 mL/min), reduce to 1 mg/kg once daily or switch to unfractionated heparin. 4