What is the recommended anticoagulation therapy for patients with Rheumatic Heart Disease (RHD) and severe Mitral Stenosis (MS)?

Anticoagulation in Rheumatic Heart Disease with Severe Mitral Stenosis

For patients with rheumatic heart disease and severe mitral stenosis, long-term vitamin K antagonist (VKA) therapy with warfarin is the mandatory treatment, targeting an INR of 2.5 (range 2.0-3.0), regardless of whether atrial fibrillation is present. 1

Anticoagulation Strategy Based on Clinical Presentation

Patients WITH Atrial Fibrillation

• VKA therapy (warfarin) is the only recommended anticoagulant with a Class I, Level C-EO recommendation from the ACC/AHA 1
• Target INR: 2.5 (range 2.0-3.0) 1, 2
• NOACs (direct oral anticoagulants) are contraindicated in rheumatic mitral stenosis, even though some registry data suggested potential benefit—these findings require further validation and current guidelines explicitly do not support NOAC use 1, 3
• The INVICTUS trial definitively showed that rivaroxaban resulted in higher event rates (including mortality) compared to VKA in patients with moderate to severe rheumatic MS and AF 4

Patients WITHOUT Atrial Fibrillation (Normal Sinus Rhythm)

The anticoagulation decision depends on specific risk factors 1:

Mandatory VKA therapy (Class 1A recommendation):

• Left atrial thrombus present 1
• Previous systemic embolism 1

VKA therapy recommended (Class 2C):

• Left atrial diameter ≥55 mm 1
• Spontaneous echo contrast in left atrium 1

No anticoagulation needed:

• Left atrial diameter <55 mm with no other risk factors 1

Warfarin Dosing and Monitoring

Initiation

• Start with 2-5 mg daily (lower doses preferred in elderly patients) 1, 3, 2
• Avoid loading doses in most patients 1
• Check INR weekly during initiation phase 3

Maintenance

• Target INR: 2.5 (range 2.0-3.0) 1, 2
• Monitor INR monthly once stable in therapeutic range 3
• Aim for time in therapeutic range (TTR) >65-70% 3
• Monitor renal and hepatic function annually 3

Higher Intensity Anticoagulation

If recurrent systemic embolism occurs despite adequate anticoagulation at INR 2.0-3.0, consider increasing target INR to 3.0 (range 2.5-3.5) or adding low-dose aspirin 75-100 mg/day 1, 2

Critical Clinical Pitfalls

Common Errors to Avoid

• Never use NOACs in rheumatic mitral stenosis—this is a Class III (Harm) recommendation despite some observational data suggesting potential benefit 1, 3
• Inadequate INR control is the primary reason for treatment failure: in one study, 21 of 24 embolic events in the warfarin group occurred when INR was <2.0 5
• Less than 30% of eligible patients maintain INR in therapeutic range in real-world settings, emphasizing the need for meticulous monitoring 6
• Aspirin monotherapy is inadequate for stroke prevention in rheumatic MS with AF—one study showed 15 embolic events with aspirin vs. only 3 with properly controlled warfarin 5

Special Considerations for Percutaneous Mitral Balloon Valvotomy (PMBV)

• If preprocedural TEE shows left atrial thrombus, postpone PMBV 1
• Administer VKA therapy with target INR 3.0 (range 2.5-3.5) until thrombus resolution documented by repeat TEE 1
• If thrombus does not resolve with VKA therapy, PMBV should not be performed 1

Mechanism of Benefit

Warfarin reduces both systemic and left atrial coagulation activity in mitral stenosis 7. Research demonstrates that anticoagulation with warfarin not only reduces systemic coagulation activity but achieves a greater reduction in left atrial coagulation activity specifically, which contributes to reduced LA thrombus formation 7. The left atrial prothrombin fragment 1+2 levels (a marker of thrombin generation) are significantly lower in patients with prolonged INR compared to normal INR 7.

Bleeding Risk Management

• Major bleeding rates with low-intensity anticoagulation (INR target 2.0) are approximately 1.25 per 100 patient-years 8
• Moderate-intensity anticoagulation (INR target 3.0) shows similar efficacy but higher bleeding rates (2.0 per 100 patient-years) without additional thromboembolic protection 8
• Minor bleeding is more frequent with higher intensity anticoagulation but major bleeding risk remains acceptable 8

Duration of Therapy

Lifelong anticoagulation is required for patients with rheumatic mitral stenosis and any of the following 1:

• Atrial fibrillation (persistent or paroxysmal)
• Left atrial thrombus
• Previous systemic embolism
• Left atrial diameter ≥55 mm