Four DOACs apixaban, dabigatran, edoxaban, and rivaroxaban have been studied in 4 large randomized trials against VKA with consistent evidence of noninferior reduction in thromboem- bolic risk and reduced bleeding risk.423 426 All trials of DOACs specifically excluded patients with val- vular AF; however, up to 20% of patients in these trials had some degree of valvular heart disease (VHD). This discrepancy has led to some confu- sion in practice, which was clarified in the 2019 AHA/ACC/Heart Rhythm Society guideline on the management of AF.32 DOACs should not be used in patients with moderately severe or greater mitral stenosis or a mechanical heart valve. 2. AF is the most common arrhythmia in the adult pop- ulation and can be categorized by the proportion of time a given patient spends in AF as paroxys- mal, persistent, or permanent. Even brief subclini- cal episodes of AF are associated with increased risk of stroke.427 Anticoagulation is recommended for patients with stroke or TIA regardless of the CLINICAL STATEMENTS AND GUIDELINES Kleindorfer amount of time spent in AF. There is no established lower limit of embolism risk from time spent in AF; furthermore, patients with AF tend to progress to greater proportions of time spent in arrhythmia over time. Moreover, up to 28% of patients are found to have AF with prolonged monitoring after stroke. Patients with a remote history of a discrete AF episode (eg, postoperative or thyrotoxicosis) represent a group at increased risk for arrhythmia but the objective risk of recur- rence is poorly defined. 3. All 4 randomized trials of DOACs demonstrated advantages to stroke risk reduction with the DOAC compared with a VKA with similar or improved stroke rates associated with similar or less bleed- ing. 