UMEM Educational Pearls

Title: Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity

Keywords: Andexanet, apixaban, rivaroxaban, factor Xa (PubMed Search)

Posted: 11/12/2015 by Bryan Hayes, PharmD
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Not to be outdone by the recent FDA approval of Idarucizumab to reverse dabigatran, a new factor Xa reversal agent is under investigation. "Andexanet binds and sequesters factor Xa inhibitors within the vascular space, thereby restoring the activity of endogenous factor Xa and reducing levels of anticoagulant activity, as assessed by measurement of thrombin generation and anti factor Xa activity, the latter of which is a direct measure of the anticoagulant activity."

Design

Two parallel randomized, placebo-controlled trials (ANNEXA-A [apixaban] and ANNEXA-R [rivaroxaban]) were conducted in healthy vounteers to evaluate the ability of andexanet to reverse anticoagulation, as measured by the percent change in anti factor Xa activity after administration.

What they Found

Compared to placebo, andexanet significantly reduced anti-factor Xa activity, increased thrombin generation, and decreased unbound drug concentration in both the apixaban and rivaroxaban groups.

Application to Clinical Practice

This drug is not yet FDA approved.
These trials were funded by the maker of andexanet (Portola Pharmaceuticals) and supported by the makers of apixaban and rivaroxaban.
Studies are needed in patients requiring urgent reversal.
The trials looked only at laboratory markers of anticoagulation. We don't know how fast (or the extent of) the reversal activity is in the clinical setting.

References

Siegal DM, et al. Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity. N Engl J Med. November 11, 2015.

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