Safe and effective stroke prevention in atrial fibrillation (AF) is crucial as 
the number of patients with this condition continues to increase. Several novel 
oral anticoagulants are being developed as replacements for warfarin for this 
indication. Direct factor Xa inhibitors comprise the largest class of oral 
anticoagulants in development; the inhibition of factor Xa is recognized to be a 
promising target for therapeutic anticoagulation, partly because of its location 
in the coagulation cascade. Apixaban, betrixaban, edoxaban, and rivaroxaban are 
small-molecule, selective inhibitors that directly and reversibly bind to the 
active site of factor Xa. Their pharmacokinetic and pharmacodynamic profiles 
vary, which might allow patient-specific therapy. Several of these agents have 
been tested in clinical trials for various indications, including AF, with 
favorable results. In particular, apixaban and rivaroxaban have shown 
superiority and noninferiority, respectively, to warfarin in phase III clinical 
trials for stroke prevention in AF. These agents have also been shown to be safe 
in terms of bleeding risk. Despite these advantages, factor Xa inhibitors have 
several characteristics, such as potential interactions with other drugs 
(inhibitors of cytochrome P450 and P-glycoprotein) and the inability to reverse 
their anticoagulant effects, as well as concerns about poor patient compliance, 
which must be considered when initiating patients on a novel factor Xa 
inhibitor.