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. In the RE-LY trial (Randomized Evaluation of Long-Term Anticoagulant Therapy), at 2 years, high-dose dabigatran was associated with lower stroke (1.11% versus 1.69%) and similar bleeding (3.11% versus 3.36%) rates compared with war- In ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation), rivaroxa- ban was noninferior to warfarin with similar rates of stroke or systemic embolism (2.1 vs 2.4 per 100 patient-years) and major bleeding (5.6% versus The ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) of 18201 patients demon- strated that apixaban was superior to warfarin at 1.8 years with fewer strokes or systemic embo- lisms (1.27% versus 1.60%) and less bleeding The ENGAGE AF-TIMI 48 trial (Global Study to Assess the Safety and Effectiveness of Edoxaban [DU-176b] vs Standard Practice of Dosing With Warfarin in Patients With Atrial Fibrillation) showed similar rates of stroke or systemic embolism with less bleeding in 21105 patients comparing 2 doses of edoxaban with war- A meta-analysis combining the data from all 4 trials found an overall 19% reduction in stroke or systemic embolism driven by a 51% reduction in hemorrhagic stroke and a 10% overall reduction in The improved safety profile of DOACs in the context of noninferior thromboembolic risk leads to the recommendation to consider prefer- ential use of a DOAC over a VKA. 4. Compared with AF, atrial flutter is a more organized macro-reentrant arrhythmia often involving the tri- cuspid isthmus. 