Atrial fibrillation (AF) is the most common cardiac arrhythmia in the developed 
world and is associated with a fivefold increase in the risk of stroke, 
accounting for up to 15% of strokes in the general population. The European 
Society of Cardiology now recommends direct oral anticoagulants, such as 
rivaroxaban, apixaban, and dabigatran, in preference to vitamin K antagonist 
therapy for the prevention of stroke in patients with A F. This review focuses 
on the direct Factor Xa inhibitor rivaroxaban, summarizing the properties that 
make rivaroxaban appropriate for anticoagulant therapy in this indication 
(including its predictable pharmacokinetic and pharmacodynamic profile and 
once-daily dosing regimen) and describing data from the Phase III ROCKET AF 
trial, which showed once-daily rivaroxaban to be noninferior to warfarin for the 
prevention of stroke in patients with nonvalvular AF. In this trial, similar 
rates of major and nonmajor clinically relevant bleeding were observed; however, 
when compared with warfarin, rivaroxaban was associated with clinically 
significant reductions in intracranial and fatal bleeding. On the basis of these 
results, rivaroxaban was approved in both the United States and the European 
Union for the prevention of stroke and systemic embolism in patients with 
nonvalvular AF. Subanalyses of ROCKET AF data showed rivaroxaban to have 
consistent efficacy and safety across a wide range of patients, and studies to 
confirm these results in real-world settings are underway. This review also 
describes practical considerations for treatment with rivaroxaban in clinical 
practice (including dose reductions in specific high-risk patients, eg, those 
with renal impairment), recommendations for the transition from vitamin K 
antagonists to rivaroxaban, the management of bleeding events, and the 
measurement of rivaroxaban exposure.