What is the recommended therapy for secondary stroke prevention in a patient with severe mitral valve regurgitation due to rheumatic fever (RF) and atrial fibrillation (a fib), who has had a stroke?

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

Warfarin with a target INR of 2.5 (range 2.0-3.0) is the definitive treatment for secondary stroke prevention in this patient with severe rheumatic mitral regurgitation and atrial fibrillation. 1, 2, 3

Primary Anticoagulation Strategy

Warfarin is mandatory for all patients with rheumatic mitral valve disease (whether stenosis or regurgitation) who have atrial fibrillation and prior stroke, regardless of the severity of the valvular lesion. 1, 2, 3 The 2023 World Stroke Organization guidelines explicitly recommend oral anticoagulation for patients with valvular atrial fibrillation (defined as mechanical valve replacement or moderate/severe mitral stenosis), and this extends to rheumatic mitral regurgitation given the underlying rheumatic pathology. 1

• The target INR should be 2.5 with an acceptable range of 2.0-3.0 for rheumatic mitral valve disease with atrial fibrillation and prior stroke. 1, 2, 3, 4
• This recommendation holds a Class IIa level of evidence from the American Heart Association/American Stroke Association, meaning it is reasonable and should be performed. 1, 3

Why NOT Apixaban or Other DOACs

Direct oral anticoagulants (DOACs) including apixaban are absolutely contraindicated in patients with rheumatic valvular heart disease. 1, 2, 3 The 2021 AHA/ASA guidelines give DOACs a Class 3: Harm recommendation in patients with mechanical heart valves and moderate to severe mitral stenosis. 1, 2

• Rheumatic heart disease represents valvular pathology that was systematically excluded from all major DOAC trials (RE-LY, ROCKET-AF, ARISTOTLE, ENGAGE AF-TIMI 48). 3, 5
• The presence of rheumatic fever as the etiology creates structural valve changes that fundamentally alter thromboembolic risk profiles, making DOAC data from non-valvular AF populations inapplicable. 2, 3, 5
• Even though this patient has mitral regurgitation rather than stenosis, the rheumatic etiology itself constitutes "valvular" disease requiring warfarin. 1, 2

Why NOT Aspirin Alone

Aspirin monotherapy is grossly inadequate for stroke prevention in rheumatic valvular disease with atrial fibrillation. 1, 6 A prospective randomized study of 229 patients with rheumatic mitral valve disease and AF demonstrated that aspirin 200 mg daily resulted in 15 embolic events compared to only 3 events in adequately anticoagulated warfarin patients (INR ≥2.0), showing clear superiority of warfarin (p < 0.0061). 6

• The 2023 World Stroke Organization guidelines explicitly state that patients suitable for anticoagulation should not receive antiplatelets for secondary stroke prevention. 1
• Aspirin reduces stroke risk by only 20% in general populations, whereas warfarin reduces thromboembolic risk by 55-67% in appropriate candidates. 1

Management of Recurrent Stroke on Warfarin

If this patient experiences another ischemic stroke while on therapeutic warfarin (INR 2.0-3.0), adding aspirin 81 mg daily to the warfarin regimen is recommended. 1, 3, 7 The AHA/ASA provides a Class IIa recommendation for adding low-dose aspirin in patients with rheumatic mitral valve disease who have recurrent embolism despite adequate warfarin therapy. 1, 3

• However, antiplatelet agents should NOT be routinely added to warfarin initially, as this increases bleeding risk without proven benefit in the absence of recurrent events. 1, 7
• The aspirin dose should be 75-100 mg daily (preferably enteric-coated 81 mg) if added for breakthrough events. 1, 3, 7

Practical Implementation Algorithm

Initiate warfarin at 2-5 mg daily without loading doses to minimize hemorrhagic complications. 2, 4 The FDA-approved warfarin labeling specifically recommends starting with 2-5 mg per day with dosage adjustments based on INR results, as large loading doses increase bleeding risk without providing faster protection. 4

• Check INR at least weekly during initiation until stable in therapeutic range (2.0-3.0). 7, 4
• Once stable, reduce monitoring frequency to at least monthly. 7
• Aim for time in therapeutic range (TTR) >65% to optimize protection against thromboembolism while minimizing bleeding. 3, 7
• Reassess renal and hepatic function at least annually, as these affect warfarin metabolism. 2

Critical Pitfalls to Avoid

Do not delay anticoagulation waiting for imaging confirmation of thrombus resolution. 3 The history of prior systemic embolism (stroke) is itself an absolute indication for anticoagulation in rheumatic mitral valve disease, independent of whether a clot is currently visible on echocardiography. 3

Do not target INR >3.0 in native rheumatic valve disease. 3, 7 The higher INR target of 2.5-3.5 is reserved only for mechanical prosthetic valves or when left atrial thrombus requires dissolution. 1, 3, 7, 4 Using unnecessarily high INR targets exponentially increases bleeding risk, particularly intracranial hemorrhage when INR exceeds 3.5. 7

Do not switch to DOACs even if INR control is difficult. 1, 2, 3 If the patient cannot maintain consistent therapeutic INR levels, the solution is more frequent monitoring and dose adjustments, not switching to a contraindicated DOAC. 2