medwireNews: Adanexanet rapidly reverses anti-factor (F)Xa activity in patients with acute major bleeding associated with FXa inhibitors, preliminary results from the ANNEXA-4 study show.
Furthermore, at 12 hours post adanexanet infusion, 79% of 47 patients who had acute major bleeding within 18 hours of FXa infusion achieved excellent or good haemostasis according to various prespecified criteria that were applied by an independent adjudication committee.
“This finding supports the idea that prolonged reversal of factor Xa inhibition may not be necessary to achieve a good hemostatic response”, say Stuart Connolly (McMaster University, Hamilton, Ontario, Canada) and co-authors of the study.
However, they caution that the study design did not allow them to determine how many patients would have achieved haemostatic efficacy without adanexanet, adding that “further refinements in the administration of adanexanet could lead to more complete reversal of anti-factor Xa activity and improved clinical outcomes.”
At a mean of 4.8 hours after emergency department presentation, all patients (mean age 77 years) received a 400 or 800 mg bolus of adanexanet, depending on the initial FXa inhibitor treatment, followed by a 480 or 960 mg, 2-hour infusion of the study drug.
For patients who had initially been treated with rivaroxaban (n=26), median FXa activity decreased by 89% from a baseline level of 277.0 ng/mL following bolus administration and by 86% at the end of the infusion. The reductions were then 39%, 49% and 64%, relative to baseline, at 4, 8 and 12 hours, respectively.
For apixaban (n=20), the initial decrease was 93% from a baseline level of 149.7 ng/mL. At 2, 4, 8 and 12 hours, decreases of 92%, 30%, 28% and 31% relative to baseline were observed.
Only one patient received enoxaparin initially, and they experienced similar reductions in FXa activity following adanexanet administration.
The majority of patients were admitted with gastrointestinal (53%) or intracranial (43%) bleeding, and the rates of excellent or good haemostatic efficacy for adanexanet were 84% and 80% in these two groups, respectively.
Connolly and team note that adanexanet treatment “was not associated with serious side effects”. Seven (15%) patients experienced thromboembolic events and seven diedwithin 30 days of treatment.
The researchers conclude in The New England Journal of Medicine: “After full enrollment in the ongoing study has provided adequate statistical power, further analysis should provide details regarding the relationship between the reduction in anti-factor Xa activity and clinical hemostatic outcomes.”
By Laura Cowen
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