Reversal of Factor Xa Inhibitors (The 2 ANNEXA Trials)

This blog reviews the article published in NEJM this week about the results of the ANNEXA trials.  ANNEXA stands for Andexanet Alfa – a Novel Antidote to the Anticoagulant Effects of FXA Inhibitors.  The study has two arms – ANNEXA-A and ANNEXA-R that looked into reversal of apixaban and rivaroxaban, respecively.

The study enrolled a small cohort of healthy older volunteers, who received either Rivaroxaban 20mg PO OD x 4 days, or Apixaban 5mg PO BID x 3.5 days to achieve steady state levels of the drug.  These volunteers were given the reversal agent Andexanet as a bolus or a bolus and infusion, or placebo.

  • ANNEXA-R:  800mg IV bolus (30mg/min) or 800mg IV bolus + 8mg/min x 2 hours [960mg total)
  • ANNEXA-A:  400mg IV bolus (30mg/min) or 400mg IV bolus + 4mg/min x 2 hours [480mg total)

The study showed that anti-factor Xa activity was reduced within 2-5 minutes, which persisted for 2 hours after administration of the drug. Thrombin generation was also demonstrated to be rapidly restored within 2-5 minutes of drug administration.

 

Mechanism of Action:  Andexanet is a recombinant modified human factor Xa decoy protein.  It is a catalytically inactive protein but is able to bind factor Xa inhibitors in the active site with high affinity.  The drug also binds and sequesters factor Xa inhibitors within the blood vessel, reducing the serum levels and reversing the effects of the anticoagulant.

Capture2

 

 

References

Siegal, Deborah M. et al. “Andexanet Alfa For The Reversal Of Factor Xa Inhibitor Activity”. New England Journal of Medicine 373.25 (2015): 2413-2424. Web.

The New England Journal of Medicine,. The ANNEXA-A And ANNEXA-R Trials.. 2015. Web. 20 Dec. 2015.

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