Anticoagulant reversal, blood pressure levels, and anticoagulant resumption in patients with anticoagulation-related intracerebral hemorrhage
Abstract
IMPORTANCE: Although use of oral anticoagulants (OACs) is increasing, there is a substantial lack of data on how to treat OAC-associated intracerebral hemorrhage (ICH). OBJECTIVE: To assess the association of anticoagulation reversal and blood pressure (BP) with hematoma enlargement and the effects of OAC resumption. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study at 19 German tertiary care centers (2006-2012) including 1176 individuals for analysis of long-term functional outcome, 853 for analysis of hematoma enlargement, and 719 for analysis of OAC resumption. EXPOSURES: Reversal of anticoagulation during acute phase, systolic BP at 4 hours, and reinitiation of OAC for long-term treatment. MAIN OUTCOMES AND MEASURES: Frequency of hematoma enlargement in relation to international normalized ratio (INR) and BP. Incidence analysis of ischemic and hemorrhagic events with or without OAC resumption. Factors associated with favorable (modified Rankin Scale score, 0-3) vs unfavorable functional outcome. RESULTS: Hemorrhage enlargement occurred in 307 of 853 patients (36.0%). Reduced rates of hematoma enlargement were associated with reversal of INR levels <1.3 within 4 hours after admission (43/217 [19.8%]) vs INR of ≥1.3 (264/636 [41.5%]; P < .001) and systolic BP <160 mm Hg at 4 hours (167/504 [33.1%]) vs ≥160 mm Hg (98/187 [52.4%]; P < .001). The combination of INR reversal <1.3 within 4 hours and systolic BP of <160 mm Hg at 4 hours was associated with lower rates of hematoma enlargement (35/193 [18.1%] vs 220/498 [44.2%] not achieving these values; OR, 0.28; 95% CI, 0.19-0.42; P < .001) and lower rates of in-hospital mortality (26/193 [13.5%] vs 103/498 [20.7%]; OR, 0.60; 95% CI, 0.37-0.95; P = .03). OAC was resumed in 172 of 719 survivors (23.9%). OAC resumption showed fewer ischemic complications (OAC: 9/172 [5.2%] vs no OAC: 82/547 [15.0%]; P < .001) and not significantly different hemorrhagic complications (OAC: 14/172 [8.1%] vs no OAC: 36/547 [6.6%]; P = .48). Propensity-matched survival analysis in patients with atrial fibrillation who restarted OAC showed a decreased HR of 0.258 (95% CI, 0.125-0.534; P < .001) for long-term mortality. Functional long-term outcome was unfavorable in 786 of 1083 patients (72.6%). CONCLUSIONS AND RELEVANCE: Among patients with OAC-associated ICH, reversal of INR <1.3 within 4 hours and systolic BP <160 mm Hg at 4 hours were associated with lower rates of hematoma enlargement, and resumption of OAC therapy was associated with lower risk of ischemic events. These findings require replication and assessment in prospective studies. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01829581.
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The available evidence indicates that anticoagulation in patients with AF can be reinitiated after 4-8 weeks, especially when the cause of bleeding or the relevant risk factor has been treated, and that such treatment leads to fewer recurrent ischaemic strokes and lower mortality.
“The available evidence indicates that anticoagulation in patients with AF can be reinitiated after 4-8 weeks, especially when the cause of bleeding or the relevant risk factor (e.g.uncontrolled hypertension) has been treated, and that such treatment leads to fewer recurrent (ischaemic) strokes and lower mortality.460,484”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [460]
Reinitiation of anticoagulation after a bleeding event is often clinically justified.
“Reinitiation of anticoagulation after a bleeding event is often clinically justified. 460, 510”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [460]
Observational data suggest that OAC can be reinitiated even after an intracerebral bleeding event.
“Observational data suggest that OAC can be reinitiated even after an intracerebral bleeding event.460,484”
From 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS (2016) · cites this paper as [460]
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2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS
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- Authors
- Kuramatsu, J. B., Gerner, S. T., Schellinger, P. D., Glahn, J., Endres, M., Sobesky, J., Flechsenhar, J., Neugebauer, H., Jüttler, E., Grau, A., Palm, F., Röther, J., Michels, P., Hamann, G. F., Hüwel, J., Hagemann, G., Barber, B., Terborg, C., Trostdorf, F., Bäzner, H., Roth, A., Wöhrle, J., Keller, M., Schwarz, M., Reimann, G., Volkmann, J., Müllges, W., Kraft, P., Classen, J., Hobohm, C., Horn, M., Milewski, A., Reichmann, H., Schneider, H., Schimmel, E., Fink, G. R., Dohmen, C., Stetefeld, H., Witte, O., Günther, A., Neumann-Haefelin, T., Racs, A. E., Nueckel, M., Erbguth, F., Kloska, S. P., Dörfler, A., Köhrmann, M., Schwab, S., & Huttner, H. B.
- Affiliations
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Johannes Wesling Klinikum Minden (DE)
- German Center for Neurodegenerative Diseases (DE)
- Charité – Universitätsmedizin Berlin (DE)
- Universität Ulm (DE)
- Klinikum Ludwigshafen (DE)
- Asklepios Klinik Altona (DE)
- Helios Dr. Horst Schmidt Kliniken Wiesbaden (DE)
- Helios Hospital Berlin-Buch (DE)
- Asklepios Klinik St. Georg (DE)
- Klinikum Stuttgart (DE)
- Department of Neurology, Community Hospital Klinikum Koblenz, Koblenz, Germany
- Klinikum Dortmund (DE)
- University of Würzburg (DE)
- Leipzig University (DE)
- Department of Neurology, Community Hospital Bad Hersfeld, Bad Hersfeld, Germany
- Technische Universität Dresden (DE)
- University of Cologne (DE)
- Friedrich Schiller University Jena (DE)
- Department of Neurology, Community Hospital Fulda, Fulda, Germany
- Klinikum Fulda (DE)
- Department of Neurology, Community Hospital Nuremberg, Nuremberg, Germany
- Nuremberg Hospital (DE)
- Corresponding author
- Huttner, Hagen B.
- ORCID
- Kuramatsu, Joji B.
- Gerner, Stefan T.
- Schellinger, Peter D.
- Endres, Matthias
- Sobesky, Jan
- Neugebauer, Hermann
- Grau, Armin
- Palm, Frederick
- Röther, Joachim
- Michels, Peter
- Hamann, Gerhard F.
- Hagemann, Georg
- Bäzner, Hansjörg
- Schwarz, Michael
- Reimann, Gernot
- Volkmann, Jens
- Müllges, Wolfgang
- Kraft, Peter
- Classen, Joseph
- Hobohm, Carsten
- Reichmann, Heinz
- Schneider, Hauke
- Fink, Gereon R.
- Dohmen, Christian
- Stetefeld, Henning
- Witte, Otto
- Günther, Albrecht
- Erbguth, Frank
- Kloska, Stephan P.
- Köhrmann, Martin
- Schwab, Stefan
- Huttner, Hagen B.
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2015-02-24
- Volume
- 313
- Issue
- 8
- Pages
- 824
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W2105908213
- Cited by
- 568
- References
- 43
- Citations by year
- 2026: 21 · 2025: 41 · 2024: 44 · 2023: 34 · 2022: 39 · 2021: 45 · 2020: 54 · 2019: 48 · 2018: 77 · 2017: 71 · 2016: 50 · 2015: 41
- FWCI
- 56.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- JuSER (Forschungszentrum Jülich) (submittedVersion)
- DZNE Pub (submittedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
- Keywords
- anticoagulant reversal, oral anticoagulants, intracerebral hemorrhage, hematoma expansion, blood pressure, international normalized ratio, functional outcome, in-hospital mortality, hemorrhagic transformation, hemorrhagic stroke, ischemic stroke, modified Rankin Scale
- MeSH terms
- Aged, Anticoagulants, Atrial Fibrillation, Blood Pressure, Cerebral Hemorrhage, Female, Hematoma, Hemorrhage, Humans, Ischemia, Male, Middle Aged, Retrospective Studies, Logistic Models, Treatment Outcome, Disease Progression, International Normalized Ratio, Stroke, Kaplan-Meier Estimate
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