Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXA Inhibitors Apixaban and Rivaroxaban - ANNEXA-A and ANNEXA-R


The goal of the two parallel trials was to evaluate treatment with andexanet alfa for the reversal of factor Xa inhibitor activity among subjects administered apixaban (ANNEXA-A) or rivaroxaban (ANNEXA-R). Currently, no agent is available to reverse the effect of the factor Xa inhibitors.

Contribution to the Literature: The ANNEXA trials showed that andexanet alfa was effective at reversing the anticoagulant effect of apixaban and rivaroxaban.

Study Design

  • Randomized
  • Parallel
  • Placebo
  • Blinded

Healthy older subjects who were administered apixaban 5 mg twice daily were randomized to andexanet alfa (n = 48) versus placebo (n = 17). Healthy older subjects who were administered rivaroxaban 20 mg daily were randomized to andexanet alfa (n = 53) versus placebo (n = 27). Andexanet alfa was given as a bolus or bolus/infusion.

  • Total number of enrollees: 145
  • Mean patient age: 58 years
  • Percentage female: 39%

Inclusion criteria:

  • Healthy subjects ages 50-75 years

Principal Findings:

Among apixaban-treated patients, anti-factor Xa activity was reduced 94% by andexanet alfa bolus vs. 21% with placebo (p < 001).

Among rivaroxaban-treated patients, anti-factor Xa activity was reduced 92% by andexanet alfa bolus vs. 18% with placebo (p < 001).

Secondary outcomes: The reversal effects were sustained when andexanet alfa was given as a bolus/infusion. There were no serious adverse or thrombotic events.


Among healthy individuals who were anticoagulated with apixaban or rivaroxaban, anti-factor Xa activity was markedly reduced with andexanet alfa bolus. The reversal of anticoagulant effect was sustained for the duration of infusion. There were no apparent adverse effects from this reversal agent. This agent represents an important antidote for patients anticoagulated with apixaban or rivaroxaban who may be suffering from a major bleeding event or who need an urgent/emergent surgical procedure.


Siegal DM, Curnutte JT, Connolly SJ, et al. Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity. N Engl J Med 2015;Nov 11:[Epub ahead of print].

Presented by Dr. Mark Crowther at the American Heart Association Scientific Sessions, Orlando, FL, November 11, 2015.

Clinical Topics: Anticoagulation Management, Dyslipidemia, Lipid Metabolism, Novel Agents

Keywords: Anticoagulants, Antidotes, Factor Xa Inhibitors, Factor Xa, AHA Annual Scientific Sessions

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