Reversal for factor Xa inhibitors

Question from patient:

Currently on dabigatran for anti-coagulation therapy. Patient stated he may be switching insurance plans which may cause him to have to switch from dabigatran to rivaroxaban or apixaban. Patient expresses concern about whether reversal agents exist for these drugs or not.

Dabigatran reversal agent -- praxbind (idarucizumab), FDA approved

Under investigation:
andexanet alfa -- antidote/reversal agent for factor Xa inhibitors (rivaroxaban, apixaban, edoxaban)

• decoy receptor -- has higher affinity to factor xa inhibitor than factor xa (binds to drug)
• not active against dabigatran
• 2015 -- first RCT:
• ages 50-75 years
• primary endpoint: % change in anti-factor xa activity measured by chromogenic assay of factor xa activity
• secondary endpoints: proportion of patients with 80% reduction in anti-factor xa activity, change in unbound inhibitor plasma concentration from baseline, change in thrombin generation
• patients either given apixaban 5 mg BID x 3.5 days (steady state) or rivaroxaban 20 mg once daily x 4 days, then randomized to andexanet alfa or placebo
• andexenet alfa given either as IV bolus or IV continuous infusion
• apixaban given bolus of 400 mg with or without continuous infusion at 4 mg/min
• rivaroxaban given bolus of 800 mg with or without continuous infusion of 8 mg/min
• results:
• anti-factor xa activity rapidly decreased within 2-5 minutes with both apixaban and rivaroxaban compared to placebo after 1 IV bolus, activity persisted for approx. 2 hours
• all patients who received full dose treatment had at least 80% reduction in anti-factor xa activity, no patients in placebo group achieved this
• conclusion: effectively and safely reversed apixaban and rivaroxaban
• was expected to be approved/released in 2016, however, in August 2016 FDA required more information from manufacturer (Portola Pharmaceuticals) regarding the manufacturing process and additional information to support inclusion of edoxaban and enoxaparin to finalize the review
• Portola is addressing these issues and re-submitting but unknown how long this will take
• phase 3b/4 study: ANNEXA-4, open label confirmatory study in patients on either apixaban, rivaroxaban, edoxaban, or enoxaparin who present with acute major bleeding
• plans to be released in 2022

Currently -- only PARTIAL reversal with either FEIBA, prothrombin complex concentrates (PCC)*four factor or recombinant factor VII