Comparative Study

. 2024 Dec 30;9(6):640-651.

doi: 10.1136/svn-2023-002813.

Intracerebral haemorrhage in patients taking different types of oral anticoagulants: a pooled individual patient data analysis from two national stroke registries

Bernhard M Siepen^{1

2}, Elisabeth Forfang^{3

4}, Mattia Branca⁵, Boudewijn Drop¹, Madlaine Mueller¹, Martina B Goeldlin¹, Mira Katan⁶, Patrik Michel⁷, Carlo Cereda⁸, Friedrich Medlin⁹, Nils Peters¹⁰, Susanne Renaud¹¹, Julien Niederhauser¹², Emmanuel Carrera¹³, Timo Kahles¹⁴, Georg Kägi^{1

15}, Manuel Bolognese¹⁶, Stephan Salmen¹⁷, Marie-Luise Mono¹⁸, Alexandros A Polymeris⁶, Susanne Wegener¹⁹, Werner Z'Graggen^{1

20}, Johannes Kaesmacher²¹, Michael Schaerer²², Biljana Rodic²³, Espen Saxhaug Kristoffersen^{24

25}, Kristin T Larsen^{3

4

24}, Torgeir Bruun Wyller^{3

4}, Bastian Volbers¹, Thomas R Meinel¹, Marcel Arnold¹, Stefan T Engelter^{6

26}, Leo H Bonati^{6

27}, Urs Fischer^{1

6}, Ole Morten Rønning^{3

24}, David J Seiffge²⁸

Affiliations

¹ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
² Graduate School for Health Sciences, University of Bern, Bern, Switzerland.
³ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁴ Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway.
⁵ CTU Bern, Department of Clinical Research, University of Bern, Bern, Switzerland.
⁶ Department of Neurology, University Hospital Basel, University of Basel, Basel, Switzerland.
⁷ Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
⁸ Stroke Center EOC, Neurocenter of Southern Switzerland, Lugano, Switzerland.
⁹ Stroke Unit and Division of Neurology, HFR Fribourg-Cantonal Hospital, Fribourg, Switzerland.
¹⁰ Stroke Center Hirslanden, Klinik Hirslanden Zurich, Zurich, Switzerland.
¹¹ Division of Neurology, Pourtalès Hospital, Neuchatel, Switzerland.
¹² Stroke Unit, GHOL, Hospital Nyon, Nyon, Switzerland.
¹³ Stroke Research Group, Department of Clinical Neurosciences, Geneva University Hospital, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
¹⁴ Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland.
¹⁵ Department of Neurology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
¹⁶ Neurology Department, Lucerne Cantonal Hospital (LUKS), Luzern, Switzerland.
¹⁷ Stroke Unit, Department of Neurology, Hospital Biel, Biel, Switzerland.
¹⁸ Department of Neurology, Stadtspitäler Triemli und Waid, Zurich, Switzerland.
¹⁹ Department of Neurology and Stroke Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
²⁰ Department of Neurosurgery, Inselspital, Bern University Hospital, Bern, Switzerland.
²¹ University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
²² Department of Neurology, Bürgerspital Solothurn, Solothurn, Switzerland.
²³ Stroke Unit, Department of Neurology, Cantonal Hospital Winterthur, Winterthur, Switzerland.
²⁴ Department of Neurology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway.
²⁵ Department of General Practice, University of Oslo, Oslo, Norway.
²⁶ Department of Neurology and Neurorehabilitation, University of Basel; University Department of Geriatric Medicine Felix Platter, University of Basel, Basel, Switzerland.
²⁷ Rehabilitation Clinic Rheinfelden, Rheinfelden, Switzerland.
²⁸ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland david.seiffge@insel.ch.

PMID: 38336370
PMCID: PMC11791643
DOI: 10.1136/svn-2023-002813

Comparative Study

Intracerebral haemorrhage in patients taking different types of oral anticoagulants: a pooled individual patient data analysis from two national stroke registries

Bernhard M Siepen et al. Stroke Vasc Neurol. 2024.

. 2024 Dec 30;9(6):640-651.

doi: 10.1136/svn-2023-002813.

Authors

Affiliations

¹ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
² Graduate School for Health Sciences, University of Bern, Bern, Switzerland.
³ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁴ Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway.
⁵ CTU Bern, Department of Clinical Research, University of Bern, Bern, Switzerland.
⁶ Department of Neurology, University Hospital Basel, University of Basel, Basel, Switzerland.
⁷ Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
⁸ Stroke Center EOC, Neurocenter of Southern Switzerland, Lugano, Switzerland.
⁹ Stroke Unit and Division of Neurology, HFR Fribourg-Cantonal Hospital, Fribourg, Switzerland.
¹⁰ Stroke Center Hirslanden, Klinik Hirslanden Zurich, Zurich, Switzerland.
¹¹ Division of Neurology, Pourtalès Hospital, Neuchatel, Switzerland.
¹² Stroke Unit, GHOL, Hospital Nyon, Nyon, Switzerland.
¹³ Stroke Research Group, Department of Clinical Neurosciences, Geneva University Hospital, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
¹⁴ Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland.
¹⁵ Department of Neurology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
¹⁶ Neurology Department, Lucerne Cantonal Hospital (LUKS), Luzern, Switzerland.
¹⁷ Stroke Unit, Department of Neurology, Hospital Biel, Biel, Switzerland.
¹⁸ Department of Neurology, Stadtspitäler Triemli und Waid, Zurich, Switzerland.
¹⁹ Department of Neurology and Stroke Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
²⁰ Department of Neurosurgery, Inselspital, Bern University Hospital, Bern, Switzerland.
²¹ University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
²² Department of Neurology, Bürgerspital Solothurn, Solothurn, Switzerland.
²³ Stroke Unit, Department of Neurology, Cantonal Hospital Winterthur, Winterthur, Switzerland.
²⁴ Department of Neurology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway.
²⁵ Department of General Practice, University of Oslo, Oslo, Norway.
²⁶ Department of Neurology and Neurorehabilitation, University of Basel; University Department of Geriatric Medicine Felix Platter, University of Basel, Basel, Switzerland.
²⁷ Rehabilitation Clinic Rheinfelden, Rheinfelden, Switzerland.
²⁸ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland david.seiffge@insel.ch.

PMID: 38336370
PMCID: PMC11791643
DOI: 10.1136/svn-2023-002813

Abstract

Background: We investigated outcomes in patients with intracerebral haemorrhage (ICH) according to prior anticoagulation treatment with Vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs) or no anticoagulation.

Methods: This is an individual patient data study combining two prospective national stroke registries from Switzerland and Norway (2013-2019). We included all consecutive patients with ICH from both registries. The main outcomes were favourable functional outcome (modified Rankin Scale 0-2) and mortality at 3 months.

Results: Among 11 349 patients with ICH (mean age 73.6 years; 47.6% women), 1491 (13.1%) were taking VKAs and 1205 (10.6%) DOACs (95.2% factor Xa inhibitors). The median percentage of patients on prior anticoagulation was 23.7 (IQR 22.6-25.1) with VKAs decreasing (from 18.3% to 7.6%) and DOACs increasing (from 3.0% to 18.0%) over time. Prior VKA therapy (n=209 (22.3%); adjusted ORs (aOR), 0.64; 95% CI, 0.49 to 0.84) and prior DOAC therapy (n=184 (25.7%); aOR, 0.64; 95% CI, 0.47 to 0.87) were independently associated with lower odds of favourable outcome compared with patients without anticoagulation (n=2037 (38.8%)). Prior VKA therapy (n=720 (49.4%); aOR, 1.71; 95% CI, 1.41 to 2.08) and prior DOAC therapy (n=460 (39.7%); aOR, 1.28; 95% CI, 1.02 to 1.60) were independently associated with higher odds of mortality compared with patients without anticoagulation (n=2512 (30.2%)).

Conclusions: The spectrum of anticoagulation-associated ICH changed over time. Compared with patients without prior anticoagulation, prior VKA treatment and prior DOAC treatment were independently associated with lower odds of favourable outcome and higher odds of mortality at 3 months. Specific reversal agents unavailable during the study period might improve outcomes of DOAC-associated ICH in the future.

Keywords: Anticoagulants; Hemorrhage; Stroke.

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Conflict of interest statement

Competing interests: MBo: personal fees from AstraZeneca, a company that produces Andexanet alfa (a specific reversal agent for factor Xa-inhibitor-associated ICH, discussed in this study). SW: consultancy fees from Bayer, a company that produces Rivaroxaban (a DOAC discussed in this study). BV: personal fees from Pfizer AG/Bristol-Myers Squibb SA and Bayer AG, producesr of Apixaban and Rivaroxaban, two drugs discussed in this study. DJS: grants from Alexion/AstraZeneca, producer of andexanet alfa discussed in this study. Personal fees from Bayer, producer of Rivaroxaban, discussed in this study. Consultancy fees from VarmX (producer of VarmX, a compound under development for the treatment of FXaI-associated bleeding). All other authors have nothing to disclose.

Figures

**Figure 1. Study patient flowchart. mRS, modified Rankin Scale.**

Figure 2. Frequency of prior anticoagulation therapy as compared with no prior anticoagulation in patients with intracerebral haemorrhage from 2013 to 2019. Combined data from Switzerland and Norway (n=11 349). The median percentage of patients on prior anticoagulation during the study period was 23.7% (IQR, 22.6–25.1) with VKAs decreasing and DOACs increasing. DOACs, direct oral anticoagulants; OACs, oral anticoagulants; VKAs, Vitamin K antagonists.

Figure 3. Functional outcome at 3 months using modified Rankin Scale (mRS) according to prior anticoagulation therapy as compared with no prior anticoagulation in patients with intracerebral haemorrhage. Combined data from Switzerland and Norway. Figure includes only sites with ≥70% availability of mRS at 3 months (49 hospitals; n=6903). Overall, prior VKA therapy (aOR, 0.64; 95% CI, 0.49 to 0.84; indicated by the continuous line) and prior DOAC therapy (aOR, 0.64; 95% CI, 0.47 to 0.87; indicated by the dashed line) were independently associated with lower odds of favourable outcome compared with patients without anticoagulation. DOACs, direct oral anticoagulants; OACs, oral anticoagulants; VKAs, Vitamin K antagonists.

See this image and copyright information in PMC

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Intracerebral haemorrhage in patients taking different types of oral anticoagulants: a pooled individual patient data analysis from two national stroke registries

Affiliations

Intracerebral haemorrhage in patients taking different types of oral anticoagulants: a pooled individual patient data analysis from two national stroke registries

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical