The anticoagulant effects of apixaban and rivaroxaban are reversed within minutes by the antidote andexanet, studies published in the NEJM show.
The two drug company sponsored studies treated 145 healthy volunteers aged 50-75 with either apixaban (5 mg twice daily) or rivaroxaban (20 mg daily).
Subjects were then randomised to andexanet given either as a bolus or as a bolus plus a two hour infusion or placebo.
Results showed that in people treated with apixaban the anti-factor Xa activity (a measure of factor Xa inhibition by the anticoagulant) was reduced by 94% in those given an andexanet bolus (24 participants) and by 21% in those randomised to placebo (9 participants) (P<0.001).
Thrombin generation was fully restored within two to five minutes in 100% of people given andexanet, compared with 11% of the placebo group (P<0.001).
Similar results were seen in study participants treated with rivaroxaban. Anti-factor Xa activity was reduced by 92% in those given an andexanet bolus (27 participants), compared with 18% of those randomised to placebo (14 participants) (P<0.001).
Thrombin generation was fully restored in 96% of the group treated with andexanet and in 7% of the placebo group (P<0.001).
These effects were sustained when participants were given a bolus of andexanet followed by an infusion.
The researchers found no serious or severe adverse events and no thrombotic events in the studies.
“The ability of andexanet to reverse anticoagulation markers in participants undergoing anticoagulation with apixaban, rivaroxaban, edoxaban or enoxaparin makes it a potential universal antidote for both direct and indirect factor Xa inhibitors,” they wrote.
An accompanying editorial cautioned that further studies were necessary to determine the dose needed in different situations.
But despite current limitations in knowledge, andexanet represented a giant step forward in our ability to control anticoagulation therapy, it concluded.