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Hemostatic Efficacy and Anti-FXa (Factor Xa) Reversal With Andexanet Alfa in Intracranial Hemorrhage: ANNEXA-4 Substudy
Andexanet alfa is a recombinant modified human FXa (factor Xa) developed to reverse FXa inhibition from anticoagulants. Hemostatic efficacy and reversal of anti-FXa activity with andexanet were assessed in patients from the ANNEXA-4 study (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effe...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140631/ https://www.ncbi.nlm.nih.gov/pubmed/33966491 http://dx.doi.org/10.1161/STROKEAHA.120.030565 |
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author | Demchuk, Andrew M. Yue, Patrick Zotova, Elena Nakamya, Juliet Xu, Lizhen Milling, Truman J. Ohara, Tomoyuki Goldstein, Joshua N. Middeldorp, Saskia Verhamme, Peter Lopez-Sendon, Jose Luis Conley, Pamela B. Curnutte, John T. Eikelboom, John W. Crowther, Mark Connolly, Stuart J. |
author_facet | Demchuk, Andrew M. Yue, Patrick Zotova, Elena Nakamya, Juliet Xu, Lizhen Milling, Truman J. Ohara, Tomoyuki Goldstein, Joshua N. Middeldorp, Saskia Verhamme, Peter Lopez-Sendon, Jose Luis Conley, Pamela B. Curnutte, John T. Eikelboom, John W. Crowther, Mark Connolly, Stuart J. |
author_sort | Demchuk, Andrew M. |
collection | PubMed |
description | Andexanet alfa is a recombinant modified human FXa (factor Xa) developed to reverse FXa inhibition from anticoagulants. Hemostatic efficacy and reversal of anti-FXa activity with andexanet were assessed in patients from the ANNEXA-4 study (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXa Inhibitors) with intracranial hemorrhage (ICrH). METHODS: ANNEXA-4 was a single-arm study evaluating andexanet in patients presenting with major bleeding ≤18 hours after taking an FXa inhibitor. Patients received a bolus plus 2-hour infusion of andexanet. Brain imaging in patients with ICrH was performed at baseline and at 1 and 12 hours postandexanet infusion. Coprimary efficacy outcomes were change in anti-FXa activity and hemostatic efficacy at 12 hours (excellent/good efficacy defined as ≤35% increase in hemorrhage volume/thickness). Safety outcomes included occurrence of thrombotic events and death at 30 days. RESULTS: A total of 227 patients with ICrH were included in the safety population (51.5% male; mean age 79.3 years) and 171 in the efficacy population (99 spontaneous and 72 traumatic bleeds). In efficacy evaluable patients, excellent/good hemostasis 12 hours postandexanet occurred in 77 out of 98 (78.6%) and in 58 out of 70 (82.9%) patients with spontaneous and traumatic bleeding, respectively. In the subanalysis by FXa inhibitor treatment group in the efficacy population, median of percent change in anti-FXa from baseline to nadir showed a decrease of 93.8% for apixaban-treated patients (n=99) and by 92.6% for rivaroxaban-treated patients (n=59). Within 30 days, death occurred in 34 out of 227 (15.0%) patients and thrombotic events occurred in 21 out of 227 (9.3%) patients (safety population). CONCLUSIONS: Andexanet reduced anti-FXa activity in FXa inhibitor-treated patients with ICrH, with a high rate of hemostatic efficacy. Andexanet may substantially benefit patients with ICrH, the most serious complication of anticoagulation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02329327. |
format | Online Article Text |
id | pubmed-8140631 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-81406312021-05-26 Hemostatic Efficacy and Anti-FXa (Factor Xa) Reversal With Andexanet Alfa in Intracranial Hemorrhage: ANNEXA-4 Substudy Demchuk, Andrew M. Yue, Patrick Zotova, Elena Nakamya, Juliet Xu, Lizhen Milling, Truman J. Ohara, Tomoyuki Goldstein, Joshua N. Middeldorp, Saskia Verhamme, Peter Lopez-Sendon, Jose Luis Conley, Pamela B. Curnutte, John T. Eikelboom, John W. Crowther, Mark Connolly, Stuart J. Stroke Original Contributions Andexanet alfa is a recombinant modified human FXa (factor Xa) developed to reverse FXa inhibition from anticoagulants. Hemostatic efficacy and reversal of anti-FXa activity with andexanet were assessed in patients from the ANNEXA-4 study (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXa Inhibitors) with intracranial hemorrhage (ICrH). METHODS: ANNEXA-4 was a single-arm study evaluating andexanet in patients presenting with major bleeding ≤18 hours after taking an FXa inhibitor. Patients received a bolus plus 2-hour infusion of andexanet. Brain imaging in patients with ICrH was performed at baseline and at 1 and 12 hours postandexanet infusion. Coprimary efficacy outcomes were change in anti-FXa activity and hemostatic efficacy at 12 hours (excellent/good efficacy defined as ≤35% increase in hemorrhage volume/thickness). Safety outcomes included occurrence of thrombotic events and death at 30 days. RESULTS: A total of 227 patients with ICrH were included in the safety population (51.5% male; mean age 79.3 years) and 171 in the efficacy population (99 spontaneous and 72 traumatic bleeds). In efficacy evaluable patients, excellent/good hemostasis 12 hours postandexanet occurred in 77 out of 98 (78.6%) and in 58 out of 70 (82.9%) patients with spontaneous and traumatic bleeding, respectively. In the subanalysis by FXa inhibitor treatment group in the efficacy population, median of percent change in anti-FXa from baseline to nadir showed a decrease of 93.8% for apixaban-treated patients (n=99) and by 92.6% for rivaroxaban-treated patients (n=59). Within 30 days, death occurred in 34 out of 227 (15.0%) patients and thrombotic events occurred in 21 out of 227 (9.3%) patients (safety population). CONCLUSIONS: Andexanet reduced anti-FXa activity in FXa inhibitor-treated patients with ICrH, with a high rate of hemostatic efficacy. Andexanet may substantially benefit patients with ICrH, the most serious complication of anticoagulation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02329327. Lippincott Williams & Wilkins 2021-05-10 2021-06 /pmc/articles/PMC8140631/ /pubmed/33966491 http://dx.doi.org/10.1161/STROKEAHA.120.030565 Text en © 2021 Portola Pharmaceuticals Inc, a subsidiary of Alexion Pharmaceuticals Inc, and the Authors. https://creativecommons.org/licenses/by-nc-nd/4.0/Stroke is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made. |
spellingShingle | Original Contributions Demchuk, Andrew M. Yue, Patrick Zotova, Elena Nakamya, Juliet Xu, Lizhen Milling, Truman J. Ohara, Tomoyuki Goldstein, Joshua N. Middeldorp, Saskia Verhamme, Peter Lopez-Sendon, Jose Luis Conley, Pamela B. Curnutte, John T. Eikelboom, John W. Crowther, Mark Connolly, Stuart J. Hemostatic Efficacy and Anti-FXa (Factor Xa) Reversal With Andexanet Alfa in Intracranial Hemorrhage: ANNEXA-4 Substudy |
title | Hemostatic Efficacy and Anti-FXa (Factor Xa) Reversal With Andexanet Alfa in Intracranial Hemorrhage: ANNEXA-4 Substudy |
title_full | Hemostatic Efficacy and Anti-FXa (Factor Xa) Reversal With Andexanet Alfa in Intracranial Hemorrhage: ANNEXA-4 Substudy |
title_fullStr | Hemostatic Efficacy and Anti-FXa (Factor Xa) Reversal With Andexanet Alfa in Intracranial Hemorrhage: ANNEXA-4 Substudy |
title_full_unstemmed | Hemostatic Efficacy and Anti-FXa (Factor Xa) Reversal With Andexanet Alfa in Intracranial Hemorrhage: ANNEXA-4 Substudy |
title_short | Hemostatic Efficacy and Anti-FXa (Factor Xa) Reversal With Andexanet Alfa in Intracranial Hemorrhage: ANNEXA-4 Substudy |
title_sort | hemostatic efficacy and anti-fxa (factor xa) reversal with andexanet alfa in intracranial hemorrhage: annexa-4 substudy |
topic | Original Contributions |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140631/ https://www.ncbi.nlm.nih.gov/pubmed/33966491 http://dx.doi.org/10.1161/STROKEAHA.120.030565 |
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