Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage
(2024) In New England Journal of Medicine 390(19). p.1745-1755- Abstract
Background Patients with acute intracerebral hemorrhage who are receiving factor Xa inhibitors have a risk of hematoma expansion. The effect of andexanet alfa, an agent that reverses the effects of factor Xa inhibitors, on hematoma volume expansion has not been well studied. Methods We randomly assigned, in a 1:1 ratio, patients who had taken factor Xa inhibitors within 15 hours before having an acute intracerebral hemorrhage to receive andexanet or usual care. The primary end point was hemostatic efficacy, defined by expansion of the hematoma volume by 35% or less at 12 hours after baseline, an increase in the score on the National Institutes of Health Stroke Scale of less than 7 points (scores range from 0 to 42, with higher scores... (More)
Background Patients with acute intracerebral hemorrhage who are receiving factor Xa inhibitors have a risk of hematoma expansion. The effect of andexanet alfa, an agent that reverses the effects of factor Xa inhibitors, on hematoma volume expansion has not been well studied. Methods We randomly assigned, in a 1:1 ratio, patients who had taken factor Xa inhibitors within 15 hours before having an acute intracerebral hemorrhage to receive andexanet or usual care. The primary end point was hemostatic efficacy, defined by expansion of the hematoma volume by 35% or less at 12 hours after baseline, an increase in the score on the National Institutes of Health Stroke Scale of less than 7 points (scores range from 0 to 42, with higher scores indicating worse neurologic deficit) at 12 hours, and no receipt of rescue therapy between 3 hours and 12 hours. Safety end points were thrombotic events and death. Results A total of 263 patients were assigned to receive andexanet, and 267 to receive usual care. Efficacy was assessed in an interim analysis that included 452 patients, and safety was analyzed in all 530 enrolled patients. Atrial fibrillation was the most common indication for factor Xa inhibitors. Of the patients receiving usual care, 85.5% received prothrombin complex concentrate. Hemostatic efficacy was achieved in 150 of 224 patients (67.0%) receiving andexanet and in 121 of 228 (53.1%) receiving usual care (adjusted difference, 13.4 percentage points; 95% confidence interval [CI], 4.6 to 22.2; P=0.003). The median reduction from baseline to the 1-to-2-hour nadir in anti-factor Xa activity was 94.5% with andexanet and 26.9% with usual care (P<0.001). Thrombotic events occurred in 27 of 263 patients (10.3%) receiving andexanet and in 15 of 267 (5.6%) receiving usual care (difference, 4.6 percentage points; 95% CI, 0.1 to 9.2; P=0.048); ischemic stroke occurred in 17 patients (6.5%) and 4 patients (1.5%), respectively. There were no appreciable differences between the groups in the score on the modified Rankin scale or in death within 30 days. Conclusions Among patients with intracerebral hemorrhage who were receiving factor Xa inhibitors, andexanet resulted in better control of hematoma expansion than usual care but was associated with thrombotic events, including ischemic stroke. (Funded by Alexion AstraZeneca Rare Disease and others; ANNEXA-I ClinicalTrials.gov number, NCT03661528.).
(Less)
- author
- author collaboration
- organization
- publishing date
- 2024-05-16
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Coagulation, Emergency Medicine, Emergency Medicine General, Hematology/Oncology, Neurology/Neurosurgery, Stroke
- in
- New England Journal of Medicine
- volume
- 390
- issue
- 19
- pages
- 11 pages
- publisher
- Massachusetts Medical Society
- external identifiers
-
- pmid:38749032
- scopus:85193355984
- ISSN
- 0028-4793
- DOI
- 10.1056/NEJMoa2313040
- language
- English
- LU publication?
- yes
- id
- b0ad56ea-51ad-40d3-9086-f5e3f75d7521
- date added to LUP
- 2024-06-03 09:13:31
- date last changed
- 2024-06-17 09:55:18
@article{b0ad56ea-51ad-40d3-9086-f5e3f75d7521,
abstract = {{<p>Background Patients with acute intracerebral hemorrhage who are receiving factor Xa inhibitors have a risk of hematoma expansion. The effect of andexanet alfa, an agent that reverses the effects of factor Xa inhibitors, on hematoma volume expansion has not been well studied. Methods We randomly assigned, in a 1:1 ratio, patients who had taken factor Xa inhibitors within 15 hours before having an acute intracerebral hemorrhage to receive andexanet or usual care. The primary end point was hemostatic efficacy, defined by expansion of the hematoma volume by 35% or less at 12 hours after baseline, an increase in the score on the National Institutes of Health Stroke Scale of less than 7 points (scores range from 0 to 42, with higher scores indicating worse neurologic deficit) at 12 hours, and no receipt of rescue therapy between 3 hours and 12 hours. Safety end points were thrombotic events and death. Results A total of 263 patients were assigned to receive andexanet, and 267 to receive usual care. Efficacy was assessed in an interim analysis that included 452 patients, and safety was analyzed in all 530 enrolled patients. Atrial fibrillation was the most common indication for factor Xa inhibitors. Of the patients receiving usual care, 85.5% received prothrombin complex concentrate. Hemostatic efficacy was achieved in 150 of 224 patients (67.0%) receiving andexanet and in 121 of 228 (53.1%) receiving usual care (adjusted difference, 13.4 percentage points; 95% confidence interval [CI], 4.6 to 22.2; P=0.003). The median reduction from baseline to the 1-to-2-hour nadir in anti-factor Xa activity was 94.5% with andexanet and 26.9% with usual care (P<0.001). Thrombotic events occurred in 27 of 263 patients (10.3%) receiving andexanet and in 15 of 267 (5.6%) receiving usual care (difference, 4.6 percentage points; 95% CI, 0.1 to 9.2; P=0.048); ischemic stroke occurred in 17 patients (6.5%) and 4 patients (1.5%), respectively. There were no appreciable differences between the groups in the score on the modified Rankin scale or in death within 30 days. Conclusions Among patients with intracerebral hemorrhage who were receiving factor Xa inhibitors, andexanet resulted in better control of hematoma expansion than usual care but was associated with thrombotic events, including ischemic stroke. (Funded by Alexion AstraZeneca Rare Disease and others; ANNEXA-I ClinicalTrials.gov number, NCT03661528.).</p>}},
author = {{Connolly, Stuart J. and Sharma, Mukul and Cohen, Alexander T. and Demchuk, Andrew M. and Członkowska, Anna and Lindgren, Arne G. and Molina, Carlos A. and Bereczki, Daniel and Toni, Danilo and Seiffge, David J. and Tanne, David and Sandset, Else Charlotte and Tsivgoulis, Georgios and Christensen, Hanne and Beyer-Westendorf, Jan and Coutinho, Jonathan M. and Crowther, Mark and Verhamme, Peter and Amarenco, Pierre and Roine, Risto O. and Mikulik, Robert and Lemmens, Robin and Veltkamp, Roland and Middeldorp, Saskia and Robinson, Thompson G. and Milling, Truman John and Tedim-Cruz, Vitor and Lang, Wilfried and Himmelmann, Anders and Ladenvall, Per and Knutsson, Mikael and Ekholm, Ella and Law, Andrew and Taylor, Amanda and Karyakina, Tetyana and Xu, Lizhen and Tsiplova, Kate and Poli, Sven and Kallmünzer, Bernd and Gumbinger, Christoph and Shoamanesh, Ashkan}},
issn = {{0028-4793}},
keywords = {{Coagulation; Emergency Medicine; Emergency Medicine General; Hematology/Oncology; Neurology/Neurosurgery; Stroke}},
language = {{eng}},
month = {{05}},
number = {{19}},
pages = {{1745--1755}},
publisher = {{Massachusetts Medical Society}},
series = {{New England Journal of Medicine}},
title = {{Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage}},
url = {{http://dx.doi.org/10.1056/NEJMoa2313040}},
doi = {{10.1056/NEJMoa2313040}},
volume = {{390}},
year = {{2024}},
}