Non-vitamin K antagonist oral anticoagulants in atrial fibrillation accompanying mitral stenosis: the concept for a trial

Abstract

Patients at thromboembolic risk with non-valvular atrial fibrillation (AF) can now be managed either with a vitamin K antagonist (VKA) or with a fixed dose of a non-VKA oral anticoagulant (NOAC), while patients with valvular AF have been restricted to VKAs on the basis of a potentially higher risk and different mechanism of thrombosis, and the lack of sufficient data on the efficacy of NOACs. The terms 'non-valvular AF' and 'valvular AF' have not been however consistently defined. 'Valvular' AF has included any valvular disorder, including valve replacement and repair. In AF with rheumatic mitral disease, observational studies strongly suggest that VKA treatment is valuable. These patients have not been included in NOAC trials, but there is also no stringent argument to have excluded them. This is at sharp variance from patients with mechanical valves, also excluded from the pivotal Phase III trial comparing warfarin with NOACs, but in whom a single Phase II trial of dabigatran etexilate against VKA treatment was stopped prematurely because of increased rates of thromboembolism as well as increased bleeding associated with dabigatran. Until more data are available, such patients should be therefore managed with VKAs. We here propose an open-label randomized trial of one of the NOACs against the best of treatment available in regions of the world in which rheumatic heart disease is still highly prevalent, aiming at showing the superiority of the NOAC used against current standard treatment.

Antithrombotic Therapy for Atrial Fibrillation

“…Also, EHRA type 1 is broadly similar to the previously described mechanical and rheumatic mitral valvular AF (MARM-AF). 444…”

Percutaneous Left Atrial Appendage Closure: is there a Role in Valvular Atrial Fibrillation

“…[21] In patients with rheumatic MS, low cardiac output with reduced transmitral flow has been implicated as a potential mechanism for increased rate of thrombus formation. [5], [22] In a study of 1544 patients with severe MS by Mahmood and colleagues, LA thrombus was identified by transesophageal echocardiogram (TEE) in 55.7% (161/289) of patients with AF and 10.2% (128/1255) of patients without AF. [23] The finding that 1 in 10 patients in the non-AF group had LA thrombus further supports the concept that rheumatic mitral valve disease may contribute to LA thrombus formation regardless of the underlying cardiac rhythm.…”

Defining nonvalvular atrial fibrillation: A quest for clarification

“…comparing NOACs to the standards of care for thromboembolic prophylaxis (antiplatelet agents or VKA) in patients with mitral stenosis. 39 They claim that a randomized, open-label, superiority trial should be conducted in specific countries with a high prevalence of mitral stenosis using a NOAC available for once daily use (rivaroxaban or edoxaban) to facilitate patients' compliance, at the same dosage used in pivotal trials in AF. The overall sample size would vary depending on the expected stroke rate, the study duration and the expected hazard ratio of stroke reduction, from around 600 to 7000.…”