Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity : Prespecified Subgroup Analysis of the ANNEXA-4 Study in Japan
AIMS: Andexanet alfa, a specific antidote to factor Xa (FXa) inhibitors, has been approved for clinical use in several countries, including Japan, based on the results from the phase 3 trial ANNEXA-4. We aimed to assess the efficacy and safety of andexanet alfa treatment in FXa inhibitor-related acute major bleeding in patients enrolled for ANNEXA-4 in Japan.
METHODS: This prespecified analysis included patients enrolled at Japanese sites in the prospective, open-label, single-arm ANNEXA-4 trial. Eligible patients had major bleeding within 18 hours of oral FXa inhibitor administration. The coprimary efficacy endpoints were percent change in anti-FXa activity and proportion of patients achieving excellent or good hemostatic efficacy 12 hours post-treatment.
RESULTS: A total of 19 patients were enrolled, all of whom had intracranial hemorrhage; 16 patients were evaluable for efficacy. Median percent reduction in anti-FXa activity from baseline to nadir was 95.4% in patients taking apixaban, 96.1% in patients taking rivaroxaban, and 82.2% in patients taking edoxaban. Overall, 14/16 patients (88%) achieved excellent or good hemostasis (apixaban, 5/5; rivaroxaban, 6/7; edoxaban, 3/4). Within 30 days, treatment-related adverse events (AEs) and serious AEs occurred in 2 and 5 patients, respectively. One patient died during follow-up, and 2 patients experienced thrombotic events.
CONCLUSION: Treatment with andexanet alfa rapidly reduced anti-FXa activity with favorable hemostatic efficacy in Japanese patients with acute major bleeding. Serious AEs of thrombotic events during rapid reversal of anti-FXa activity arose as particular safety concerns in this population as with previous studies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:31 |
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| Enthalten in: |
Journal of atherosclerosis and thrombosis - 31(2024), 3 vom: 01. März, Seite 201-213 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Toyoda, Kazunori [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 05.03.2024 Date Revised 09.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.5551/jat.64223 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM361331789 |
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| 100 | 1 | |a Toyoda, Kazunori |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity |b Prespecified Subgroup Analysis of the ANNEXA-4 Study in Japan |
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| 500 | |a Date Completed 05.03.2024 | ||
| 500 | |a Date Revised 09.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a AIMS: Andexanet alfa, a specific antidote to factor Xa (FXa) inhibitors, has been approved for clinical use in several countries, including Japan, based on the results from the phase 3 trial ANNEXA-4. We aimed to assess the efficacy and safety of andexanet alfa treatment in FXa inhibitor-related acute major bleeding in patients enrolled for ANNEXA-4 in Japan | ||
| 520 | |a METHODS: This prespecified analysis included patients enrolled at Japanese sites in the prospective, open-label, single-arm ANNEXA-4 trial. Eligible patients had major bleeding within 18 hours of oral FXa inhibitor administration. The coprimary efficacy endpoints were percent change in anti-FXa activity and proportion of patients achieving excellent or good hemostatic efficacy 12 hours post-treatment | ||
| 520 | |a RESULTS: A total of 19 patients were enrolled, all of whom had intracranial hemorrhage; 16 patients were evaluable for efficacy. Median percent reduction in anti-FXa activity from baseline to nadir was 95.4% in patients taking apixaban, 96.1% in patients taking rivaroxaban, and 82.2% in patients taking edoxaban. Overall, 14/16 patients (88%) achieved excellent or good hemostasis (apixaban, 5/5; rivaroxaban, 6/7; edoxaban, 3/4). Within 30 days, treatment-related adverse events (AEs) and serious AEs occurred in 2 and 5 patients, respectively. One patient died during follow-up, and 2 patients experienced thrombotic events | ||
| 520 | |a CONCLUSION: Treatment with andexanet alfa rapidly reduced anti-FXa activity with favorable hemostatic efficacy in Japanese patients with acute major bleeding. Serious AEs of thrombotic events during rapid reversal of anti-FXa activity arose as particular safety concerns in this population as with previous studies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Anticoagulation | |
| 650 | 4 | |a Antidote | |
| 650 | 4 | |a Asian | |
| 650 | 4 | |a Bleeding | |
| 650 | 4 | |a Intracranial hemorrhage | |
| 650 | 7 | |a Factor Xa Inhibitors |2 NLM | |
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| 650 | 7 | |a Hemostatics |2 NLM | |
| 650 | 7 | |a Fibrinolytic Agents |2 NLM | |
| 650 | 7 | |a Recombinant Proteins |2 NLM | |
| 650 | 7 | |a Anticoagulants |2 NLM | |
| 650 | 7 | |a Pyridines |2 NLM | |
| 650 | 7 | |a Thiazoles |2 NLM | |
| 700 | 1 | |a Arakawa, Shuji |e verfasserin |4 aut | |
| 700 | 1 | |a Ezura, Masayuki |e verfasserin |4 aut | |
| 700 | 1 | |a Kobayashi, Rei |e verfasserin |4 aut | |
| 700 | 1 | |a Tanaka, Yoshihide |e verfasserin |4 aut | |
| 700 | 1 | |a Hasegawa, Shu |e verfasserin |4 aut | |
| 700 | 1 | |a Yamashiro, Shigeo |e verfasserin |4 aut | |
| 700 | 1 | |a Komatsu, Yoji |e verfasserin |4 aut | |
| 700 | 1 | |a Terasawa, Yuka |e verfasserin |4 aut | |
| 700 | 1 | |a Masuno, Tomohiko |e verfasserin |4 aut | |
| 700 | 1 | |a Kobayashi, Hiroshi |e verfasserin |4 aut | |
| 700 | 1 | |a Oikawa, Suzuko |e verfasserin |4 aut | |
| 700 | 1 | |a Yasaka, Masahiro |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of atherosclerosis and thrombosis |d 1997 |g 31(2024), 3 vom: 01. März, Seite 201-213 |w (DE-627)NLM091773172 |x 1880-3873 |7 nnns |
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