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Direct oral anticoagulants versus no anticoagulation for the prevention of stroke in survivors of intracerebral haemorrhage with atrial fibrillation (PRESTIGE-AF): a multicentre, open-label, randomised, phase 3 trial

Veltkamp, R. ; Norrving, B. LU and Heuschmann, P.U. (2025) In The Lancet 405(10482). p.927-936
Abstract
Background: Direct oral anticoagulants (DOACs) reduce the rate of thromboembolism in patients with atrial fibrillation but the benefits and risks in survivors of intracerebral haemorrhage are uncertain. We aimed to determine whether DOACs reduce the risk of ischaemic stroke without substantially increasing the risk of recurrent intracerebral haemorrhage. Methods: PRESTIGE-AF is a multicentre, open-label, randomised, phase 3 trial conducted at 75 hospitals in six European countries. Eligible patients were aged 18 years or older with spontaneous intracerebral haemorrhage, atrial fibrillation, an indication for anticoagulation, and a score of 4 or less on the modified Rankin Scale. Patients were randomly assigned (1:1) to a DOAC or no... (More)
Background: Direct oral anticoagulants (DOACs) reduce the rate of thromboembolism in patients with atrial fibrillation but the benefits and risks in survivors of intracerebral haemorrhage are uncertain. We aimed to determine whether DOACs reduce the risk of ischaemic stroke without substantially increasing the risk of recurrent intracerebral haemorrhage. Methods: PRESTIGE-AF is a multicentre, open-label, randomised, phase 3 trial conducted at 75 hospitals in six European countries. Eligible patients were aged 18 years or older with spontaneous intracerebral haemorrhage, atrial fibrillation, an indication for anticoagulation, and a score of 4 or less on the modified Rankin Scale. Patients were randomly assigned (1:1) to a DOAC or no anticoagulation, stratified by intracerebral haemorrhage location and sex. Only the events adjudication committee was masked to treatment allocation. The coprimary endpoints were first ischaemic stroke and first recurrent intracerebral haemorrhage. Hierarchical testing for superiority and non-inferiority, respectively, was performed in the intention-to-treat population. The margin to establish non-inferiority regarding intracerebral haemorrhage was less than 1·735. The safety analysis was done in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT03996772, and is complete. Findings: Between May 31, 2019, and Nov 30, 2023, 319 participants were enrolled and 158 were randomly assigned to the DOAC group and 161 to the no anticoagulant group. Patients' median age was 79 years (IQR 73–83). 113 (35%) of 319 patients were female and 206 (65%) were male. Median follow-up was 1·4 years (IQR 0·7–2·3). First ischaemic stroke occurred less frequently in the DOAC group than in the no anticoagulant group (hazard ratio [HR] 0·05 [95% CI 0·01–0·36]; log-rank p (Less)
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author
; and
author collaboration
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The Lancet
volume
405
issue
10482
pages
10 pages
publisher
Elsevier
external identifiers
  • scopus:105000047337
  • pmid:40023176
ISSN
0140-6736
DOI
10.1016/S0140-6736(25)00333-2
language
English
LU publication?
yes
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Number of authors = 51 EID = 105000047337 Start page = 927 End page = 936 Affiliation = Veltkamp R., Department of Brain Sciences, Imperial College London, London, United Kingdom, Department of Neurology, Alfried-Krupp Krankenhaus, Essen, Germany, Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany Affiliation = Wolfe C.D.A., School of Life Course and Population Sciences, King's College London, London, United Kingdom, NIHR Applied Research Collaboration South London, London, United Kingdom Affiliation = Heuschmann P.U., Clinical Trial Center Würzburg, University Hospital Würzburg, Würzburg, Germany, Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany, Institute for Medical Data Science, University Hospital Würzburg, Würzburg, Germany
id
351c65a1-9933-49b8-bed9-dd78c1eb4f90
date added to LUP
2025-12-17 14:32:45
date last changed
2025-12-18 03:00:10
@article{351c65a1-9933-49b8-bed9-dd78c1eb4f90,
  abstract     = {{Background: Direct oral anticoagulants (DOACs) reduce the rate of thromboembolism in patients with atrial fibrillation but the benefits and risks in survivors of intracerebral haemorrhage are uncertain. We aimed to determine whether DOACs reduce the risk of ischaemic stroke without substantially increasing the risk of recurrent intracerebral haemorrhage. Methods: PRESTIGE-AF is a multicentre, open-label, randomised, phase 3 trial conducted at 75 hospitals in six European countries. Eligible patients were aged 18 years or older with spontaneous intracerebral haemorrhage, atrial fibrillation, an indication for anticoagulation, and a score of 4 or less on the modified Rankin Scale. Patients were randomly assigned (1:1) to a DOAC or no anticoagulation, stratified by intracerebral haemorrhage location and sex. Only the events adjudication committee was masked to treatment allocation. The coprimary endpoints were first ischaemic stroke and first recurrent intracerebral haemorrhage. Hierarchical testing for superiority and non-inferiority, respectively, was performed in the intention-to-treat population. The margin to establish non-inferiority regarding intracerebral haemorrhage was less than 1·735. The safety analysis was done in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT03996772, and is complete. Findings: Between May 31, 2019, and Nov 30, 2023, 319 participants were enrolled and 158 were randomly assigned to the DOAC group and 161 to the no anticoagulant group. Patients' median age was 79 years (IQR 73–83). 113 (35%) of 319 patients were female and 206 (65%) were male. Median follow-up was 1·4 years (IQR 0·7–2·3). First ischaemic stroke occurred less frequently in the DOAC group than in the no anticoagulant group (hazard ratio [HR] 0·05 [95% CI 0·01–0·36]; log-rank p}},
  author       = {{Veltkamp, R. and Norrving, B. and Heuschmann, P.U.}},
  issn         = {{0140-6736}},
  language     = {{eng}},
  number       = {{10482}},
  pages        = {{927--936}},
  publisher    = {{Elsevier}},
  series       = {{The Lancet}},
  title        = {{Direct oral anticoagulants versus no anticoagulation for the prevention of stroke in survivors of intracerebral haemorrhage with atrial fibrillation (PRESTIGE-AF): a multicentre, open-label, randomised, phase 3 trial}},
  url          = {{http://dx.doi.org/10.1016/S0140-6736(25)00333-2}},
  doi          = {{10.1016/S0140-6736(25)00333-2}},
  volume       = {{405}},
  year         = {{2025}},
}