Selecting an Anticoagulant Regimen Balancing Risks and Benefits (Modified From Section 4.1.1., Selecting an Antithrombotic Regimen Balancing Risks and Benefits, in the 2014 AF Guideline) Introductory Text The distinction between nonvalvular and valvular AF has confused clinicians, varying among AF clinical tri- als of non vitamin K oral anticoagulants (NOACs) (ie, dabigatran [a direct thrombin inhibitor] and rivaroxa- ban, apixaban, and edoxaban [factor Xa inhibitors]; also referred to as direct-acting oral anticoagulants [DOACs]) and between North American and Europe- an AF guidelines. Valvular AF generally refers to AF in the setting of moderate-to-severe mitral stenosis (potentially requiring surgical intervention) or in the presence of an artificial (mechanical) heart valve. Val- vular AF is considered an indication for long-term anticoagulation with warfarin. In contrast, nonvalvu- lar AF does not imply the absence of valvular heart disease. Instead, as used in the present focused up- date, nonvalvular AF is AF in the absence of mod- erate-to-severe mitral stenosis or a mechanical heart valve. This is because in most AF NOAC clinical trials, up to approximately 20% of patients were enrolled with various valvular defects, including mild mitral stenosis, mitral regurgitation, aortic stenosis, aortic regurgitation, and tricuspid regurgitation;S4.1.1-1,S4.1.1-2 some trials enrolled small numbers of patients with valve repair, valvuloplasty, and bioprosthetic valves. Furthermore, meta-analysis derived data from the original clinical trials suggest that, among patients with AF and these valvular lesions and operations, NOACs reduce stroke and systemic embolism com- pared with warfarin, but with differences in bleed- For recommendations from the 2014 AF guideline that were modified only to define the exclusion criteria for valvular AF or to change anti- thrombotic to anticoagulant, LOE and supportive text have not been updated. A fifth NOAC, betrixa- ban, has not been approved by the FDA for use in patients with AF. 