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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 Branca  5 , Boudewijn Drop  1 , Madlaine Mueller  1 , Martina B Goeldlin  1 , Mira Katan  6 , Patrik Michel  7 , Carlo Cereda  8 , Friedrich Medlin  9 , Nils Peters  10 , Susanne Renaud  11 , Julien Niederhauser  12 , Emmanuel Carrera  13 , Timo Kahles  14 , Georg Kägi  1   15 , Manuel Bolognese  16 , Stephan Salmen  17 , Marie-Luise Mono  18 , Alexandros A Polymeris  6 , Susanne Wegener  19 , Werner Z'Graggen  1   20 , Johannes Kaesmacher  21 , Michael Schaerer  22 , Biljana Rodic  23 , Espen Saxhaug Kristoffersen  24   25 , Kristin T Larsen  3   4   24 , Torgeir Bruun Wyller  3   4 , Bastian Volbers  1 , Thomas R Meinel  1 , Marcel Arnold  1 , Stefan T Engelter  6   26 , Leo H Bonati  6   27 , Urs Fischer  1   6 , Ole Morten Rønning  3   24 , David J Seiffge  28
Affiliations
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. .

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
Figure 1. Study patient flowchart. mRS, modified Rankin Scale.
Figure 2
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
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.
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