Oral factor Xa inhibitors for the prevention of stroke in atrial fibrillation.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA. jonathan.piccini@duke.edu
Jonathan P
JP
Piccini
Renato D
RD
Lopes
Kenneth W
KW
Mahaffey
D000925:Anticoagulants / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications*; D001549:Benzamides / Q000627:therapeutic use; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D009025:Morpholines / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D011728:Pyridones / Q000627:therapeutic use; D000069552:Rivaroxaban; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D013844:Thiazoles / Q000627:therapeutic use; D013876:Thiophenes / Q000627:therapeutic use; D013923:Thromboembolism / Q000209:etiology / Q000517:prevention & control*; D014859:Warfarin / Q000627:therapeutic use
D000925:Anticoagulants; D001549:Benzamides; D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D009025:Morpholines; D011720:Pyrazoles; D011725:Pyridines; D011728:Pyridones; D013844:Thiazoles; D013876:Thiophenes; C522181:apixaban; D014859:Warfarin; C543086:betrixaban; D000069552:Rivaroxaban; C552171:edoxaban