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JAMA. 2015 Feb 24;313(8):824-36. doi: 10.1001/jama.2015.0846.

Anticoagulant reversal, blood pressure levels, and anticoagulant resumption in patients with anticoagulation-related intracerebral hemorrhage.

Author information

1
Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.
2
Department of Neurology and Neurogeriatry, Community Hospital Johannes Wesling Klinikum Minden, Minden, Germany.
3
Department of Neurology, University of Berlin-Charité, Berlin, Germany4Center for Stroke Research Berlin, Berlin, Germany5German Centre for Cardiovascular Research (DZHK), Berlin, Germany6German Center for Neurodegenerative Diseases (DZNE), Charité-Univer.
4
Department of Neurology, University of Berlin-Charité, Berlin, Germany.
5
Department of Neurology, University of Berlin-Charité, Berlin, Germany7Department of Neurology, University of Ulm, Ulm, Germany.
6
Department of Neurology, Community Hospital Klinikum der Stadt Ludwigshafen am Rhein, Ludwigshafen, Germany.
7
Department of Neurology, Community Hospital Asklepios Klinik Hamburg Altona, Hamburg, Germany.
8
Department of Neurology, Community Hospital Dr Horst Schmidt Klinikum Wiesbaden, Wiesbaden, Germany.
9
Department of Neurology, Community Hospital Helios Klinikum Berlin-Buch, Berlin, Germany.
10
Department of Neurology, Community Hospital Asklepios Klinik St Georg, Hamburg, Germany.
11
Department of Neurology, Community Hospital Klinikum Stuttgart, Stuttgart, Germany.
12
Department of Neurology, Community Hospital Klinikum Koblenz, Koblenz, Germany.
13
Department of Neurology, Community Hospital Klinikum Dortmund, Dortmund, Germany.
14
Department of Neurology, University of Würzburg, Würzburg, Germany.
15
Department of Neurology, University of Würzburg, Würzburg, Germany17Institute of Clinical Epidemiology and Biometry, Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.
16
Department of Neurology, University of Leipzig, Leipzig, Germany.
17
Department of Neurology, Community Hospital Bad Hersfeld, Bad Hersfeld, Germany.
18
Department of Neurology, University of Dresden, Dresden, Germany.
19
Department of Neurology, University of Cologne, Cologne, Germany.
20
Department of Neurology, University of Jena, Jena, Germany.
21
Department of Neurology, Community Hospital Fulda, Fulda, Germany.
22
Department of Neurology, Community Hospital Nuremberg, Nuremberg, Germany.
23
Department of Neuroradiology, University of Erlangen-Nuremberg, Erlangen, Germany.

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.

PMID:
25710659
DOI:
10.1001/jama.2015.0846
[Indexed for MEDLINE]

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