Bleeding Outcomes in Patients Treated With Asundexian in Phase II Trials
Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved..
BACKGROUND: Phase II trials of asundexian were underpowered to detect important differences in bleeding.
OBJECTIVES: The goal of this study was to obtain best estimates of effects of asundexian vs active control/placebo on major and clinically relevant nonmajor (CRNM) and all bleeding, describe most common sites of bleeding, and explore association between asundexian exposure and bleeding.
METHODS: We performed a pooled analysis of 3 phase II trials of asundexian in patients with atrial fibrillation (AF), recent acute myocardial infarction (AMI), or stroke. Bleeding was defined according to the International Society on Thrombosis and Hemostasis (ISTH) criteria.
RESULTS: In patients with AF (n = 755), both asundexian 20 mg and 50 mg once daily vs apixaban had fewer major/CRNM events (3 of 249; incidence rate [IR] per 100 patient-years 5.47 vs 1 of 254 [IR: not calculable] vs 6 of 250 [IR: 11.10]) and all bleeding (12 of 249 [IR: 22.26] vs 10 of 254 [IR: 18.21] vs 26 of 250 [IR: 50.56]). In patients with recent AMI or stroke (n = 3,409), asundexian 10 mg, 20 mg, and 50 mg once daily compared with placebo had similar rates of major/CRNM events (44 of 840 [IR: 7.55] vs 42 of 843 [IR: 7.04] vs 56 of 845 [IR: 9.63] vs 41 of 851 [IR: 6.99]) and all bleeding (107 of 840 [IR: 19.57] vs 123 of 843 [IR: 22.45] vs 130 of 845 [IR: 24.19] vs 129 of 851 [IR: 23.84]). Most common sites of major/CRNM bleeding with asundexian were gastrointestinal, respiratory, urogenital, and skin. There was no significant association between asundexian exposure and major/CRNM bleeding.
CONCLUSIONS: Analyses of phase II trials involving >500 bleeds highlight the potential for improved safety of asundexian compared with apixaban and similar safety compared with placebo. Further evidence on the efficacy of asundexian awaits the results of ongoing phase III trials.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:83 |
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| Enthalten in: |
Journal of the American College of Cardiology - 83(2024), 6 vom: 13. Feb., Seite 669-678 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Eikelboom, John W [VerfasserIn] |
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| Links: |
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| Themen: |
Anticoagulants |
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| Anmerkungen: |
Date Completed 09.02.2024 Date Revised 09.02.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1016/j.jacc.2023.12.004 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368152316 |
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| 100 | 1 | |a Eikelboom, John W |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Bleeding Outcomes in Patients Treated With Asundexian in Phase II Trials |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Completed 09.02.2024 | ||
| 500 | |a Date Revised 09.02.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a BACKGROUND: Phase II trials of asundexian were underpowered to detect important differences in bleeding | ||
| 520 | |a OBJECTIVES: The goal of this study was to obtain best estimates of effects of asundexian vs active control/placebo on major and clinically relevant nonmajor (CRNM) and all bleeding, describe most common sites of bleeding, and explore association between asundexian exposure and bleeding | ||
| 520 | |a METHODS: We performed a pooled analysis of 3 phase II trials of asundexian in patients with atrial fibrillation (AF), recent acute myocardial infarction (AMI), or stroke. Bleeding was defined according to the International Society on Thrombosis and Hemostasis (ISTH) criteria | ||
| 520 | |a RESULTS: In patients with AF (n = 755), both asundexian 20 mg and 50 mg once daily vs apixaban had fewer major/CRNM events (3 of 249; incidence rate [IR] per 100 patient-years 5.47 vs 1 of 254 [IR: not calculable] vs 6 of 250 [IR: 11.10]) and all bleeding (12 of 249 [IR: 22.26] vs 10 of 254 [IR: 18.21] vs 26 of 250 [IR: 50.56]). In patients with recent AMI or stroke (n = 3,409), asundexian 10 mg, 20 mg, and 50 mg once daily compared with placebo had similar rates of major/CRNM events (44 of 840 [IR: 7.55] vs 42 of 843 [IR: 7.04] vs 56 of 845 [IR: 9.63] vs 41 of 851 [IR: 6.99]) and all bleeding (107 of 840 [IR: 19.57] vs 123 of 843 [IR: 22.45] vs 130 of 845 [IR: 24.19] vs 129 of 851 [IR: 23.84]). Most common sites of major/CRNM bleeding with asundexian were gastrointestinal, respiratory, urogenital, and skin. There was no significant association between asundexian exposure and major/CRNM bleeding | ||
| 520 | |a CONCLUSIONS: Analyses of phase II trials involving >500 bleeds highlight the potential for improved safety of asundexian compared with apixaban and similar safety compared with placebo. Further evidence on the efficacy of asundexian awaits the results of ongoing phase III trials | ||
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a apixaban | |
| 650 | 4 | |a asundexian | |
| 650 | 4 | |a atrial fibrillation | |
| 650 | 4 | |a bleeding | |
| 650 | 4 | |a myocardial infarction | |
| 650 | 4 | |a placebo | |
| 650 | 4 | |a stroke | |
| 650 | 7 | |a Anticoagulants |2 NLM | |
| 650 | 7 | |a Pyridones |2 NLM | |
| 700 | 1 | |a Mundl, Hardi |e verfasserin |4 aut | |
| 700 | 1 | |a Alexander, John H |e verfasserin |4 aut | |
| 700 | 1 | |a Caso, Valeria |e verfasserin |4 aut | |
| 700 | 1 | |a Connolly, Stuart J |e verfasserin |4 aut | |
| 700 | 1 | |a Coppolecchia, Rosa |e verfasserin |4 aut | |
| 700 | 1 | |a Gebel, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Hart, Robert G |e verfasserin |4 aut | |
| 700 | 1 | |a Holberg, Gerlind |e verfasserin |4 aut | |
| 700 | 1 | |a Keller, Lars |e verfasserin |4 aut | |
| 700 | 1 | |a Patel, Manesh R |e verfasserin |4 aut | |
| 700 | 1 | |a Piccini, Jonathan P |e verfasserin |4 aut | |
| 700 | 1 | |a Rao, Sunil V |e verfasserin |4 aut | |
| 700 | 1 | |a Shoamanesh, Ashkan |e verfasserin |4 aut | |
| 700 | 1 | |a Tamm, Miriam |e verfasserin |4 aut | |
| 700 | 1 | |a Viethen, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Yassen, Ashraf |e verfasserin |4 aut | |
| 700 | 1 | |a Bonaca, Marc P |e verfasserin |4 aut | |
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