What is the efficacy of factor Xa inhibitors for stroke prevention in patients with atrial fibrillation (AF)?

Updated: Dec 18, 2018
  • Author: Salvador Cruz-Flores, MD, MPH, FAHA, FCCM, FAAN, FACP, FANA; Chief Editor: Helmi L Lutsep, MD  more...
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Apixaban (Eliquis) was approved by the FDA in December 2012. Approval was based on 2 clinical trials. The ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial compared apixaban with warfarin for the prevention of stroke or systemic embolism in patients with atrial fibrillation and at least one additional risk factor for stroke. Results showed that apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality. [25]

Rivaroxaban (Xarelto) was approved in 2011 to reduce the risk of stroke and systemic embolism in patients with nonvalvular AF. Approval was based on the ROCKET-AF double-blind trial (n >14,000), in which the risk of major bleeding was similar for rivaroxaban and warfarin, but a significantly lower risk of intracranial hemorrhage and fatal bleeding was seen with rivaroxaban when compared with warfarin. [33]

Edoxaban (Savaysa) was approved by the FDA in January 2015 to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. In the ENGAGE AF-TIMI 48 trial (n=21,105), edoxaban was noninferior to warfarin with respect to the prevention of stroke or systemic embolism. Edoxaban was associated with significantly lower rates of major bleeding (P < 0.001) and death from cardiovascular causes (P=0.01%) compared with warfarin. [29]

In May 2018, coagulation factor Xa recombinant (AndexXa) was approved for patients treated with rivaroxaban or apixaban, when reversal of anticoagulation is needed because of life-threatening or uncontrolled bleeding. Approval was supported by data from two Phase 3 ANNEXA studies (ANNEXA-R and ANNEXA-A), which evaluated the safety and efficacy of Andexxa in reversing the anticoagulant activity of the Factor Xa inhibitors rivaroxaban and apixaban in healthy older volunteers. Results demonstrated a rapid and significant reversal of anti-Factor Xa (FXa) activity. Anti-FXa activity was reduced among apixaban-treated participants by 94% compared with 21% for placebo (p< 0.001). A 92% reduction of anti-FXa activity was observed in the rivaroxaban-treated participants compared with 18% for placebo (p< 0.001). [34]

In the ANNEXA-4 trial, 67 patients who had acute major bleeding within 18 hours after administration of an FXa inhibitor received coagulation factor Xa recombinant. After the IV bolus plus 2-hour IV infusion, the median anti-FXa activity decreased by 89% from baseline among patients receiving rivaroxaban and by 93% among patients receiving apixaban. Assessment at 12 hours after the infusion adjudicated clinical hemostasis as excellent or good in 37 of 47 patients in the efficacy analysis (79%; 95% CI, 64 to 89). Thrombotic events occurred in 12 of 67 patients (18%) during the 30-day follow-up. [35]

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