In a patient with severe rheumatic mitral valve regurgitation and atrial fibrillation, which medication is appropriate for secondary stroke prevention?

Warfarin is Mandatory for Secondary Stroke Prevention in Rheumatic Mitral Regurgitation with Atrial Fibrillation

In a patient with severe rheumatic mitral valve regurgitation and atrial fibrillation who has already had a stroke, warfarin with a target INR of 2.0-3.0 is the only appropriate anticoagulant for secondary stroke prevention—apixaban and other DOACs are contraindicated, and aspirin is inadequate. 1

Why Warfarin is Required

Rheumatic valve disease categorically excludes DOAC use. The 2021 AHA/ASA Stroke Prevention Guidelines explicitly state that DOACs are recommended for nonvalvular atrial fibrillation, but patients with moderate-to-severe mitral stenosis or rheumatic valve disease fall under "valvular AF" and require warfarin therapy with a target INR of 2.0-3.0. 2 This applies to all rheumatic valve disease, including rheumatic mitral regurgitation, not just stenosis. 1

The American College of Cardiology explicitly contraindicates DOACs in patients with rheumatic valve disease and atrial fibrillation, mandating warfarin instead. 1 The 2023 World Stroke Organization guidelines reinforce this, stating that patients with valvular atrial fibrillation (mechanical valve replacement or moderate/severe mitral stenosis) require oral anticoagulation—and by extension, this applies to rheumatic valve disease of any type. 2

Why Apixaban is Contraindicated

No randomized trial has ever evaluated DOACs in rheumatic valve disease. All landmark DOAC trials (ARISTOTLE for apixaban, RE-LY for dabigatran, ROCKET-AF for rivaroxaban) specifically excluded patients with rheumatic valve disease. 3 The use of apixaban in this setting is off-label and potentially unsafe. 1

While subanalyses suggest DOACs may be safe in non-rheumatic mitral regurgitation, aortic stenosis, and aortic regurgitation, patients with moderate-to-severe mitral stenosis or mechanical valves must continue warfarin. 3 Rheumatic valve disease carries unique pathophysiology—chronic inflammation, fibrosis, and altered atrial substrate—that may not respond to DOACs the same way as nonvalvular AF. 4

Why Aspirin is Inadequate

Aspirin reduces stroke risk by only 19-22% compared with placebo, whereas warfarin reduces stroke risk by 62-64%. 1 In atrial fibrillation with rheumatic valve disease, this modest benefit is grossly insufficient for a high-risk population. 1

The 2011 AHA/ASA guidelines state that for patients with ischemic stroke or TIA and rheumatic mitral valve disease, long-term warfarin therapy with an INR target of 2.5 (range 2.0-3.0) is reasonable, whether or not AF is present—and antiplatelet agents should not be routinely added to warfarin to avoid additional bleeding risk. 2 Current guidelines advise against antiplatelet therapy when oral anticoagulation is indicated for atrial fibrillation with valvular disease. 1

Warfarin Dosing and Monitoring

Initiate warfarin at 2-5 mg daily (lower doses for elderly or debilitated patients), with dosage adjustments based on PT/INR. 5 Avoid loading doses, as they increase hemorrhagic complications without providing faster protection. 5

Target INR is 2.5 (range 2.0-3.0) for rheumatic mitral regurgitation with atrial fibrillation. 2, 1 Check INR weekly during initiation, then monthly once stable in the therapeutic range. 1, 5 If the patient spends less than 65-70% of time in therapeutic range, intensify monitoring and patient education rather than switching to a DOAC, which remains contraindicated. 1

Common Pitfalls to Avoid

• Do not use apixaban or any DOAC in rheumatic valve disease, even if the patient has difficulty maintaining therapeutic INR with warfarin—the solution is better warfarin management, not switching to a contraindicated agent. 1
• Do not add aspirin to warfarin unless there is a specific indication (e.g., mechanical mitral valve with prior stroke despite adequate anticoagulation), as this increases bleeding risk without clear benefit in rheumatic mitral regurgitation. 2
• Do not underestimate stroke risk in rheumatic valve disease with AF—the annual stroke rate is approximately 4%, making anticoagulation absolutely essential. 4