Management of Atrial Fibrillation: Direct Factor IIa and Xa Inhibitors or “Warfarin Shotgun”?

Abstract

Nonvalvular atrial fibrillation increases in prevalence with age and often requires long-term oral anticoagulation to prevent ischemic stroke. Vitamin K antagonists are highly effective for stroke prevention. However, suboptimal risk assessment, variability in response, drug and food interactions, and monitoring requirements result in underprescription of warfarin by physicians and poor adherence to therapy by patients. In addition, the vitamin K antagonists modulate coagulation by inhibiting multiple coagulation factors (factors II, VII, IX, and X). New oral direct factor IIa and Xa inhibitors offer improved risk-benefit profiles, simplifying thromboprophylaxis and overcoming some practical barriers to long-term therapy. Their potential benefit is a function of targeting specific activated factors produced at key junctions of the coagulation system. However, important questions about patient management with these new agents have not been fully answered by studies completed to date and clinical inertia must yet be overcome.