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Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors
Stuart J Connolly1, Mark Crowther1, John W Eikelboom1
1From the Population Health Research Institute (S.J.C., J.W.E., D.M.S., E.Z., B.M., S.A., J.N.) and the Department of Medicine (M. Crowther), McMaster University, Hamilton, ON, and the University of Calgary, Calgary, AB (A.M.D.) - all in Canada; Harvard Medical School (C.M.G.) and Brigham and Women's Hospital (D.J.P.) - both in Boston; Portola Pharmaceuticals, South San Francisco, CA (J.T.C., J.H.L., P.Y., M.D.B., G.L., P.B.C., S.G., J.L., S.S.); University of Leuven, Leuven, Belgium (P.V.); Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand (J.S.), and Grenoble-Alpes University Hospital, Grenoble (P.A.) - both in France; Academic Medical Center, Amsterdam (S.M.); Guy's and St. Thomas' Hospitals, King's College London, London (A.T.C.); University Hospital Carl Gustav Carus Dresden, Dresden, Germany (J.B.-W.); Instituto de Investigación Hospital Universitario La Paz, Madrid (J.L.-S.); Sarasota Memorial Hospital, Sarasota, FL (M. Concha); and Seton Dell Medical School Stroke Institute, Austin, TX (T.J.M.).
Andexanet alfa effectively reversed factor Xa inhibitors in patients with major bleeding, achieving good or excellent hemostasis in 82%. This reversal agent offers a critical option for managing bleeding complications from these anticoagulants.
Area of Science:
- Pharmacology
- Hematology
- Clinical Medicine
Background:
- Andexanet alfa is a modified recombinant inactive form of human factor Xa.
- It is designed to reverse the anticoagulant effects of factor Xa inhibitors.
Purpose of the Study:
- To evaluate the efficacy and safety of andexanet alfa in patients experiencing acute major bleeding while on factor Xa inhibitors.
- To assess the reduction in anti-factor Xa activity and the rate of hemostatic efficacy.
Main Methods:
- A study involving 352 patients with acute major bleeding within 18 hours of factor Xa inhibitor administration.
- Patients received a bolus of andexanet alfa followed by a 2-hour infusion.
- Coprimary outcomes included percent change in anti-factor Xa activity and hemostatic efficacy at 12 hours post-infusion.
Main Results:
- In patients receiving apixaban or rivaroxaban, andexanet alfa significantly reduced median anti-factor Xa activity by 92%.
- Excellent or good hemostasis was achieved in 82% of evaluable patients.
- Within 30 days, 14% of patients died and 10% experienced a thrombotic event.
Conclusions:
- Andexanet alfa markedly reduced anti-factor Xa activity in patients with acute major bleeding.
- The agent demonstrated excellent or good hemostatic efficacy in 82% of patients.
- The study was funded by Portola Pharmaceuticals and registered as ANNEXA-4 (NCT02329327).
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