Factor Xa inhibitors: a novel therapeutic class for the treatment of nonvalvular atrial fibrillation

Abstract

Atrial fibrillation is the most common cause of stroke. Treatment with anticoagulants in patients with atrial fibrillation reduces embolic complications of the disease including stroke. However, the commonly used anticoagulant has a narrow therapeutic index, requires routine monitoring, and has numerous drug and food interactions leading to less than optimal rates of adherence. Inhibition of clotting factor Xa has been evaluated as a potential target for anticoagulation therapy with the hypothesis that using target-specific therapy will alleviate some of the dosing variability observed with the vitamin K antagonist. Three factor Xa inhibitors are currently indicated for use in nonvalvular atrial fibrillation. Similar to the vitamin K antagonist, warfarin, all of the factor Xa inhibitors are administered orally. Rivaroxaban and edoxaban are dosed once daily while apixaban is dosed twice daily. All three agents have demonstrated noninferiority when compared with current standard treatment with warfarin for efficacy and safety outcomes. The therapeutic dose of factor Xa inhibitors vary based on renal function. Unlike warfarin, there are no currently available antidotes for the factor Xa inhibitors although this is an area of interest for current and future studies. In the event of a life-threatening bleed there are established management strategies to reverse the bleeding effects of the factor Xa inhibitors.