BACKGROUND: Bleeding is a complication of treatment with @entity6236 inhibitors, but there are no specific agents for the reversal of the effects of these drugs. Andexanet is designed to reverse the anticoagulant effects of @entity6236 inhibitors. METHODS: Healthy older volunteers were given 5 mg of @entity5424 twice daily or 20 mg of @entity3925 daily. For each @entity6236 inhibitor, a two-part randomized placebo-controlled study was conducted to evaluate andexanet administered as a bolus or as a bolus plus a 2-hour infusion. The primary outcome was the mean percent change in anti- @entity6236 activity, which is a measure of @entity6236 inhibition by the anticoagulant. RESULTS: Among the @entity5424 -treated participants, anti- @entity6236 activity was reduced by 94% among those who received an andexanet bolus (24 @entity1 ), as compared with 21% among those who received placebo (9 @entity1 ) (P<0.001), and unbound @entity5424 concentration was reduced by 9.3 ng per milliliter versus 1.9 ng per milliliter (P<0.001); @entity556 generation was fully restored in 100% versus 11% of the @entity1 (P<0.001) within 2 to 5 minutes. Among the @entity3925 -treated participants, anti- @entity6236 activity was reduced by 92% among those who received an andexanet bolus (27 @entity1 ), as compared with 18% among those who received placebo (14 @entity1 ) (P<0.001), and unbound @entity3925 concentration was reduced by 23.4 ng per milliliter versus 4.2 ng per milliliter (P<0.001); @entity556 generation was fully restored in 96% versus 7% of the @entity1 (P<0.001). These effects were sustained when andexanet was administered as a bolus plus an infusion. In a subgroup of @entity1 , transient increases in levels of d-dimer and prothrombin fragments 1 and 2 were observed, which resolved within 24 to 72 hours. No serious adverse or @entity715 events were reported. CONCLUSIONS: Andexanet reversed the anticoagulant activity of @entity5424 and @entity3925 in older healthy @entity1 within minutes after administration and for the duration of infusion, without evidence of clinical toxic effects. (Funded by Portola Pharmaceuticals and others; ANNEXA-A and ANNEXA-R ClinicalTrials.gov numbers, NCT02207725 and NCT02220725.).

Andexanet Alfa for the Reversal of XXXX Inhibitor Activity.

@entity1 :: ('9606', 'Species') :: ['participants'] @entity556 :: ('2147', 'Gene') :: ['thrombin'] @entity3925 :: ('MESH:C503223', 'Chemical') :: ['rivaroxaban'] @entity5424 :: ('MESH:C522181', 'Chemical') :: ['apixaban'] @entity715 :: ('MESH:D013927', 'Disease') :: ['thrombotic'] @entity6236 :: ('2159', 'Gene') :: ['factor Xa']
@entity6236 :: (2159,Gene) :: ['Factor Xa']
