Prevention of Stroke in Intracerebral Haemorrhage Survivors with Atrial Fibrillation: Rationale and Design for PRESTIGE-AF Trial

Eleni Korompoki^{1

2}, Peter Heuschmann^{3

4}, Kirsten H Harvey¹, Cornelia Fiessler⁴, Uwe Malzahn⁴, Klemens Hügen⁴, Sabine Ullmann⁴, Gabriele Putz Todd⁴, Carolin Schuhmann⁴, Joan Montaner^{5

6}, Igor Sibon^{7

8}, Stephanie Debette^{9

10}, Christian Enzinger¹¹, Stefan Ropele¹¹, Viktoria Rücker³, Kirsten Haas³, Emily Harvey¹, Charles Wolfe^{12

13}, Yanzhong Wang¹², Peter B Nielsen^{14

15}, Valeria Caso¹⁶, Gregory Y H Lip^{14

17}, Deirdre A Lane^{14

17

18}, Omid Halse^{1

19}, Peter Ringleb²⁰, Walter E Haefeli^{21

22}, Kathrin I Foerster²¹, Viktoria S Wurmbach^{21

22}, Roland Veltkamp^{1

20

23}; PRESTIGE-AF investigators

Affiliations

¹ Department of Brain Sciences, Imperial College London, London, United Kingdom.
² Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Alexandra Hospital, Athens, Greece.
³ Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany.
⁴ Clinical Trial Center Würzburg, University Hospital Würzburg, Würzburg, Germany.
⁵ Department of Neurology, Institute de Biomedicine of Seville, IBiS/Hospital Universitario Virgen del Rocío/CSIC/University of Seville, Hospital Universitario Virgen Macarena, Seville, Spain.
⁶ Neurovascular Research Laboratory, Vall d'Hebron Institute of Research (VHIR), Hospital Vall d'Hebron, Barcelona, Spain.
⁷ University Bordeaux, UMR-CNRS 5287, INCIA, Bordeaux, France.
⁸ Bordeaux University Hospital, Stroke Unit, Bordeaux, France.
⁹ UMR 1219 Bordeaux Population Health Center, University Bordeaux, Bordeaux, France.
¹⁰ Department of Neurology, Institute for Neurodegenerative Diseases, Bordeaux University Hospital, Bordeaux, France.
¹¹ Department of Neurology, Medical University of Graz, Graz, Austria.
¹² School of Life Course and Population Sciences, King's College London, London, United Kingdom.
¹³ NIHR Applied Research Collaboration (ARC) South London, London, United Kingdom.
¹⁴ Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark.
¹⁵ Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.
¹⁶ Stroke Unit - Internal, Vascular and Emergency Medicine, University of Perugia, Santa Maria della Misericordia Hospital Perugia, Perugia, Italy.
¹⁷ Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom.
¹⁸ Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom.
¹⁹ Department of Stroke and Neuroscience, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom.
²⁰ Department of Neurology, University Heidelberg, Heidelberg, Germany.
²¹ Internal Medicine IX - Department of Clinical Pharmacology and Pharmacoepidemiology, Cooperation Unit Clinical Pharmacy, Heidelberg University Hospital, Heidelberg, Germany.
²² Internal Medicine IX Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Heidelberg, Germany.
²³ Department of Neurology, Alfried-Krupp Krankenhaus, Essen, Germany.

PMID: 39740761
PMCID: PMC11961226
DOI: 10.1055/a-2496-5492

Prevention of Stroke in Intracerebral Haemorrhage Survivors with Atrial Fibrillation: Rationale and Design for PRESTIGE-AF Trial

Eleni Korompoki et al. Thromb Haemost. 2025 Apr.

. 2025 Apr;125(4):395-403.

doi: 10.1055/a-2496-5492. Epub 2024 Dec 31.

Authors

Affiliations

¹ Department of Brain Sciences, Imperial College London, London, United Kingdom.
² Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Alexandra Hospital, Athens, Greece.
³ Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany.
⁴ Clinical Trial Center Würzburg, University Hospital Würzburg, Würzburg, Germany.
⁵ Department of Neurology, Institute de Biomedicine of Seville, IBiS/Hospital Universitario Virgen del Rocío/CSIC/University of Seville, Hospital Universitario Virgen Macarena, Seville, Spain.
⁶ Neurovascular Research Laboratory, Vall d'Hebron Institute of Research (VHIR), Hospital Vall d'Hebron, Barcelona, Spain.
⁷ University Bordeaux, UMR-CNRS 5287, INCIA, Bordeaux, France.
⁸ Bordeaux University Hospital, Stroke Unit, Bordeaux, France.
⁹ UMR 1219 Bordeaux Population Health Center, University Bordeaux, Bordeaux, France.
¹⁰ Department of Neurology, Institute for Neurodegenerative Diseases, Bordeaux University Hospital, Bordeaux, France.
¹¹ Department of Neurology, Medical University of Graz, Graz, Austria.
¹² School of Life Course and Population Sciences, King's College London, London, United Kingdom.
¹³ NIHR Applied Research Collaboration (ARC) South London, London, United Kingdom.
¹⁴ Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark.
¹⁵ Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.
¹⁶ Stroke Unit - Internal, Vascular and Emergency Medicine, University of Perugia, Santa Maria della Misericordia Hospital Perugia, Perugia, Italy.
¹⁷ Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool John Moores University and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom.
¹⁸ Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom.
¹⁹ Department of Stroke and Neuroscience, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom.
²⁰ Department of Neurology, University Heidelberg, Heidelberg, Germany.
²¹ Internal Medicine IX - Department of Clinical Pharmacology and Pharmacoepidemiology, Cooperation Unit Clinical Pharmacy, Heidelberg University Hospital, Heidelberg, Germany.
²² Internal Medicine IX Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Heidelberg, Germany.
²³ Department of Neurology, Alfried-Krupp Krankenhaus, Essen, Germany.

PMID: 39740761
PMCID: PMC11961226
DOI: 10.1055/a-2496-5492

Abstract

Adequate secondary prevention in survivors of intracerebral hemorrhage (ICH) who also have atrial fibrillation (AF) is a long-standing clinical dilemma because these patients are at increased risk of recurrent ICH as well as of ischemic stroke. The efficacy and safety of oral anticoagulation, the standard preventive medication for ischemic stroke patients with AF, in ICH patients with AF are uncertain. PRESTIGE-AF is an international, phase 3b, multi-center, randomized, open, blinded end-point assessment (PROBE) clinical trial that compared the efficacy and safety of direct oral anticoagulants (DOACs) with no DOAC (either no antithrombotic treatment or any antiplatelet drug). Randomization occurred in a 1:1 ratio and stratification was based on ICH location and sex. The two co-primary binary endpoints included ischemic stroke and recurrent ICH which will be analyzed hierarchically according to the intention-to-treat principle. Secondary efficacy endpoints encompassed all-stroke and systemic embolism, all-cause and cardiovascular mortality, major adverse cardiac events, and net clinical benefit. Secondary safety endpoints included any major hemorrhage and intracranial hemorrhage. All outcome events were adjudicated by an independent committee. Results of PRESTIGE-AF are expected to support risk-adjusted secondary prevention in ICH survivors with AF and to inform clinical guideline recommendations.

The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).

PubMed Disclaimer

Conflict of interest statement

All the authors are a part of European Union's Horizon 2020 research and innovation program under grant agreement No. 754517 (PRESTIGE-AF). E.K. received Speaker Honoraria/Advisory boards/Travel grants from Amgen, AstraZeneca, Bayer, Elpen, Innovis, Pfizer, Sanofi. All outside the submitted work. P.H. received Institutional Research Grants by German Ministry of Research and Education, German Research Foundation, Federal Joint Committee (G-BA) within the Innovation fond, German Cancer Aid, German Heart Foundation, Bavarian State, Robert Koch Institute, University Hospital Heidelberg. Y.W. received support from The National Institute for Health and Care Research (NIHR) under its Program Grants for Applied Research (NIHR202339). P.B.N. received Institutional support by grants of Daiichi Sankyo; Consultancy: Daiichi-Sankoy, Bayer; Speaker Honoraria/Advisory boards: SERVIER, Baye. V.C. received consultancy fees from Bayer Steering Committee Oceanic AF; Speakers: Bayer, BMS-Pfizer alliance and Daiichi-Sankyo. Leadership Role: WSO Treasurer. D.L. received institutional support for investigator-initiated quality improvement grants: Bristol-Myers Squibb and Pfizer; Speaker: Bayer, Boehringer Ingelheim, and Bristol-Myers Squibb/Pfizer; Consultancy: Bristol-Myers Squibb and Boehringer Ingelheim; all outside the submitted work. P.R. received institution support by: Boehringer Ingelheim, Bayer; Speaker: Boehringer Ingelheim, Bayer, Pfizer. Participation on Data Safety: CLOSURE-AF (Institution) NISCI (no payment). W.H. received institutional support by grants from Boehringer Ingelheim and Daiichi-Sankyo. R. V. received speaker Honoraria/Advisory boards: AstraZeneca, Bayer, BMS-Pfizer alliance. Research support: Bayer, BMS-Pfizer alliance, Boehringer Ingelheim, Daiichi Sankyo, Medtronic, Biogen. All other authors declare no conflict of interest.

Figures

**Fig. 1**
Trial flowchart. AF, atrial fibrillation; ICH, intracerebral hemorrhage.

See this image and copyright information in PMC

References

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1. Global Burden of Diseases, Injuries, Risk Factors Study 2010 (GBD 2010) ; GBD Stroke Experts Group . Krishnamurthi R V, Feigin V L, Forouzanfar M H et al.Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990-2010: findings from the Global Burden of Disease Study 2010. Lancet Glob Health. 2013;1(05):e259–e281. - PMC - PubMed
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1. Flaherty M L, Kissela B, Woo D et al.The increasing incidence of anticoagulant-associated intracerebral hemorrhage. Neurology. 2007;68(02):116–121. - PubMed

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Prevention of Stroke in Intracerebral Haemorrhage Survivors with Atrial Fibrillation: Rationale and Design for PRESTIGE-AF Trial

Affiliations

Prevention of Stroke in Intracerebral Haemorrhage Survivors with Atrial Fibrillation: Rationale and Design for PRESTIGE-AF Trial

Authors

Affiliations

Abstract

Conflict of interest statement

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References

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Medical