In a series of patients with stroke and AF evaluated by echocardiography, 90% of identified thrombus was seen in the left atrial appendage.432 Anti- coagulation decreases thrombus formation systemically, including the left atrium, and reduces the risk of stroke or systemic embolism in AF, but at the cost of increased bleeding. Four approved direct-acting oral anticoagu- lants (DOACs) have been studied in large randomized trials and shown to clinically reduce the risk of throm- botic stroke with less bleeding risk compared with vita- min K antagonists (VKAs). Patients with stroke or TIA represent a higher-risk population for recurrent stroke events than the overall population studied in the largest randomized trials. Moreover, when considering use of the -VASc risk calculators,420,439,440 the presence of stroke or TIA places a patient in a category in which anticoagulation is recommended regardless of other risk factors. Recommendation-Specific Supportive Text 1. The risk of thromboembolism from AF is reduced by anticoagulation. VKA with warfarin reduced the primary event rate in the randomized SPAF trial (Stroke Prevention in Atrial Fibrillation Study) by 67% (7.4% to 2.3%) and was superior to treat- ment with aspirin alone, which reduced the primary event rate by 42%.419 Subsequent studies using risk characterization scores have further supported the effectiveness of VKAs in reducing stroke risk Furthermore, in all scoring systems of stroke risk in AF, prior stroke or TIA alone places a patient in a risk category in which anticoagulation is recommended. 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). 