Use of Direct Oral Anticoagulants in Patients With Atrial Fibrillation and Valvular Heart Lesions

A trial fibrillation (AF) is the most common cardiac arrhythmia. It was estimated to affect up to 6.1 million Americans in 2010, and since AF is more common with increasing age, it is predicted to affect 12.1 million in the United States by 2030. AF increases the risk of stroke 5-fold across all age groups, and AF-related stroke incidence ranges from <1% to >20% per year in the absence of anticoagulation. AF is implicated in 15% of all strokes in the United States. Stroke prevention is central to the management of patients with AF. For many years, the use of oral anticoagulant therapy with warfarin, described as a vitamin K antagonist (VKA), has been the standard therapy for the prevention of thromboembolism in patients with AF. Warfarin is an inexpensive and effective therapeutic; however, its use is complicated by a narrow therapeutic window, which makes it difficult to maintain patients within a defined anticoagulation range. Additionally, warfarin is associated with numerous drug and dietary interactions, and its susceptibility to genetic variations makes dosage requirements vary widely among individuals. Regular blood monitoring and dose adjustment are necessary to maintain the international normalized ratio within the target therapeutic range. The introduction of direct oral anticoagulants (DOACs) has expanded the therapeutic options for primary and secondary stroke prevention in patients with nonvalvular AF (NVAF). Unlike warfarin, DOACs act through the direct inhibition of coagulation factors thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban, and edoxaban). DOACs do not require routine monitoring or dose adjustment and they have short half-lives, no food interactions, and relatively few drug interactions, which makes them more convenient alternatives to warfarin to reduce the risk of stroke and systemic embolism (SSE). However, in contrast to warfarin, no specific reversal agents are available for the management of bleeding events during anticoagulation therapy with factor Xa inhibitors. Idarucizumab has recently been approved by the US Food and Drug Administration for the reversal of dabigatran. Idarucizumab is a humanized monoclonal antibody fragment indicated in dabigatran-treated patients when reversal of the anticoagulant effects of dabigatran is needed for emergency surgery or urgent procedures and in lifethreatening or uncontrolled bleeding. Idarucizumab received accelerated approval based on a reduction in unbound dabigatran and normalization of coagulation parameters in healthy volunteers. Other reversal agents, including a recombinant protein for the reversal of factor Xa inhibitors and a small synthetic molecule for the reversal of all DOACs, are in development. To date, dabigatran, rivaroxaban, apixaban, and edoxaban have each been approved in the United States to reduce the risk of SSE in patients with NVAF as well as for the treatment of deep vein thrombosis and pulmonary embolism. Large randomized controlled trials have assessed the efficacy and safety of the 4 approved DOACs for the prevention of SSE in patients with NVAF. The design of these trials was based on historic randomized controlled trials of adjusted-dose warfarin therapy for stroke prevention in patients with AF, which generally excluded patients with severe or moderate mitral stenosis and prosthetic heart valves. DOACs were associated with a similar or lower risk of SSE compared with warfarin. Additionally, rates of major and intracranial bleeding with any DOAC were similar to or lower than the rates with warfarin. As these studies established the efficacy and safety of DOACs to reduce the risk of SSE in patients with NVAF, they generally excluded patients with mitral stenosis or artificial heart valves or valve repair. However, they commonly included patients with other types of valvular heart disease (VHD), including mitral regurgitation, From the Albert Einstein College of Medicine at Montefiore Hospital, Bronx, NY; Department of Biomedical Engineering, University of Texas at Austin, TX; Texas Cardiac Arrhythmia Institute at St. David’s Medical Center, Austin, TX; Department of Cardiology, University of Foggia, Foggia, Italy. Correspondence to: Luigi Di Biase, MD, PhD, FACC, FHRS, Albert Einstein College of Medicine at Montefiore Hospital, 111 E 210 St, Bronx, NY 10467. E-mail: [email protected] J Am Heart Assoc. 2016;5:e002776 doi: 10.1161/JAHA.115.002776. a 2016 The Author. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.