PURPOSE OF REVIEW: Prevention of stroke and systemic emboli is paramount in the 
management of atrial fibrillation. Although warfarin is the predominant 
anticoagulant used in patients with atrial fibrillation, it has significant 
limitations that have impeded appropriate use of stroke prophylaxis in eligible 
patients with atrial fibrillation. Consequently, much research has been focused 
on finding an alternative to warfarin. We review the potential alternatives in 
development and evaluate the current evidence concerning their safety and 
efficacy.
RECENT FINDINGS: Oral direct factor Xa inhibitors are potentially well tolerated 
and effective replacements for warfarin. These agents do not require cofactors 
and offer selective inhibition at a critical step of amplification in the 
coagulation cascade. Multiple direct anti-factor Xa agents are currently 
undergoing evaluation in phase I, II, and III trials. Early results suggest that 
these novel anticoagulants have favorable pharmacokinetic and pharmacodynamic 
profiles with minimal-to-no requirements for therapeutic monitoring. Two direct 
factor Xa inhibitors are emerging from phase II trials (betrixaban and YM150) 
and three are being evaluated in phase III trials (apixaban, edoxaban, and 
rivaroxaban) for the prevention of stroke and systemic emboli in patients with 
atrial fibrillation. The phase III trials of apixaban and rivaroxaban have 
completed enrollment and are in the follow-up phase.
SUMMARY: Given the growing population of patients with atrial fibrillation, 
there is a great interest in finding new therapies for oral anticoagulation. The 
direct factor Xa inhibitors may offer several promising alternatives to warfarin 
therapy.