What is the level of evidence for recommending anticoagulation with warfarin (International Normalized Ratio (INR) anticoagulant) in patients with non-rheumatic moderate mitral stenosis and atrial fibrillation?

From the Guidelines

Anticoagulation with warfarin is recommended for patients with non-rheumatic moderate mitral stenosis and atrial fibrillation, based on the exclusion criteria defined in the 2020 update to the 2016 ACC/AHA clinical performance and quality measures for adults with atrial fibrillation or atrial flutter 1. The level of evidence for this recommendation is Class I, Level of Evidence A for the use of warfarin in patients with mechanical heart valves, but for patients with moderate or severe mitral stenosis, the evidence is not as clear. However, according to the 2020 update, DOACs are recommended over warfarin in DOAC-eligible patients with AF, except with moderate or severe mitral stenosis or a mechanical heart valve 1. This implies that warfarin may still be the preferred option for patients with moderate mitral stenosis and atrial fibrillation, although the level of evidence is not explicitly stated for this specific population. The target INR should be maintained between 2.0 and 3.0, with regular monitoring every 1-4 weeks depending on INR stability, as recommended in the 2020 update 1. It's also important to consider the patient's individual risk factors and preferences when making decisions about anticoagulant therapy, as recommended in the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation 1. In general, the benefit of stroke prevention with anticoagulation substantially outweighs the bleeding risk in most patients with atrial fibrillation and mitral stenosis. The 2011 guidelines for the prevention of stroke in patients with stroke or transient ischemic attack also provide some guidance on the use of anticoagulation in patients with native valvular heart disease, including mitral stenosis 1. However, the most recent and highest-quality evidence comes from the 2020 update, which should be prioritized when making clinical decisions 1. Key points to consider when prescribing warfarin include:

• Regular monitoring of INR levels
• Education on potential drug-food interactions
• Bridging with heparin during initiation of therapy or temporary warfarin discontinuation
• Individualized decision-making based on patient risk factors and preferences.

From the FDA Drug Label

For patients with AF and mitral stenosis, anticoagulation with oral warfarin is recommended (7th ACCP) Oral anticoagulation therapy has not been evaluated by properly designed clinical trials in patients with valvular disease associated with atrial fibrillation, patients with mitral stenosis, and patients with recurrent systemic embolism of unknown etiology.

The level of evidence for recommending anticoagulation with warfarin in patients with non-rheumatic moderate mitral stenosis and atrial fibrillation is based on recommendations from the 7th American College of Chest Physicians (ACCP) guidelines 2, 2.

• The recommendation is based on expert opinion and guidelines, rather than direct evidence from clinical trials.
• The guidelines suggest anticoagulation with oral warfarin for patients with AF and mitral stenosis.
• However, there is a lack of direct evidence from properly designed clinical trials in patients with valvular disease associated with atrial fibrillation, including those with mitral stenosis. Therefore, the level of evidence is low to moderate, and the recommendation should be considered with caution.

From the Research

Level of Evidence for Anticoagulation Recommendation

The level of evidence for recommending anticoagulation with warfarin (International Normalized Ratio (INR) anticoagulant) in patients with non-rheumatic moderate mitral stenosis and atrial fibrillation is based on several studies:

• A 2003 study 3 found that low intensity anticoagulation (target INR = 2) was effective and safe in high-risk patients with mitral stenosis and atrial fibrillation.
• A 2004 study 4 evaluated the efficacy and safety of combined therapy with antiplatelet and moderate-intensity anticoagulation in patients with atrial fibrillation associated with recognized risk factors or mitral stenosis, but did not specifically investigate mitral stenosis patients.
• A 2019 study 5 found that direct oral anticoagulants (DOACs) were effective and safe in patients with mitral stenosis and atrial fibrillation, with a lower rate of thromboembolic events compared to warfarin.
• A 2020 study protocol 6 aims to evaluate the safety and efficacy of dabigatran for stroke prevention in atrial fibrillation patients with moderate or severe mitral stenosis.
• A 2016 review 7 discussed the use of oral anticoagulation in patients with end-stage renal disease (ESRD) and atrial fibrillation, but did not specifically address mitral stenosis.

Key Findings

• Low intensity anticoagulation (target INR = 2) is effective and safe in patients with mitral stenosis and atrial fibrillation 3.
• DOACs may be a promising alternative to warfarin in patients with mitral stenosis and atrial fibrillation, with a lower rate of thromboembolic events 5.
• The safety and efficacy of dabigatran in patients with moderate or severe mitral stenosis and atrial fibrillation are being investigated in an ongoing study 6.

Study Limitations

• The 2003 study 3 had a relatively small sample size and a single-center design.
• The 2004 study 4 did not specifically investigate mitral stenosis patients.
• The 2019 study 5 was a retrospective analysis and had a limited sample size.
• The 2020 study protocol 6 is ongoing and has not yet reported results.
• The 2016 review 7 did not specifically address mitral stenosis.