Stroke prevention in atrial fibrillation (AF) has been challenging over decades, 
mostly due to a number of difficulties associated with oral vitamin K 
antagonists (VKAs), which have been the most effective stroke prevention 
treatment for a long time. The oral direct thrombin inhibitors (e.g., 
dabigatran) and oral direct inhibitors of factor Xa (e.g., rivaroxaban, 
apixaban) have emerged recently as an alternative to VKAs for stroke prevention 
in AF. These drugs act rapidly, and have a predictable and stable dose-related 
anticoagulant effect with a few clinically relevant drug-drug interactions. The 
novel oral anticoagulants are used in fixed doses with no need for regular 
laboratory monitoring of anticoagulation intensity. However, each of these drugs 
has distinct pharmacological properties that could influence optimal use in 
clinical practice. The following phase 3 randomized trials with novel oral 
anticoagulants versus warfarin for stroke prevention in AF have been completed: 
the Randomized Evaluation of Long-term Anticoagulant therapy (RE-LY) trial with 
dabigatran, the Rivaroxaban Once daily oral direct Factor Xa inhibition Compared 
with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial 
Fibrillation (ROCKET-AF) trial with rivaroxaban, and the Apixaban for Reduction 
of Stroke and Other Thromboembolism Events in Atrial Fibrillation (ARISTOTLE) 
trial with apixaban. Moreover, the Apixaban Versus Acetylsalicylic Acid to 
prevent Strokes (AVERROES) trial included patients with AF who have failed or 
were unsuitable for warfarin, and compared apixaban versus aspirin for stroke 
prevention in AF. Overall, apixaban has two large trials for stroke prevention 
in AF showing benefits not only over warfarin, but also over aspirin among those 
patients who have failed or refused warfarin. In the ARISTOTLE trial, apixaban 
was superior to warfarin in the reduction of stroke or systemic embolism, major 
bleeding, intracranial hemorrhage, and all-cause mortality, with a similar 
reduction in the rate of ischemic stroke and better tolerability. When compared 
with aspirin in the AVERROES trial, apixaban was associated with more effective 
reduction of stroke, a similar risk of major bleeding, and better tolerability. 
In this review article, the authors summarize the current knowledge on novel 
oral anticoagulants and discuss the clinical aspects of their use for stroke 
prevention in AF, with particular emphasis on apixaban.