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Original Investigation
February 24, 2015

Anticoagulant Reversal, Blood Pressure Levels, and Anticoagulant Resumption in Patients With Anticoagulation-Related Intracerebral Hemorrhage

Author Affiliations
  • 1Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany
  • 2Department of Neurology and Neurogeriatry, Community Hospital Johannes Wesling Klinikum Minden, Minden, Germany
  • 3Department of Neurology, University of Berlin–Charité, Berlin, Germany
  • 4Center for Stroke Research Berlin, Berlin, Germany
  • 5German Centre for Cardiovascular Research (DZHK), Berlin, Germany
  • 6German Center for Neurodegenerative Diseases (DZNE), Charité-Universitätsmedizin Berlin, Berlin, Germany
  • 7Department of Neurology, University of Ulm, Ulm, Germany
  • 8Department of Neurology, Community Hospital Klinikum der Stadt Ludwigshafen am Rhein, Ludwigshafen, Germany
  • 9Department of Neurology, Community Hospital Asklepios Klinik Hamburg Altona, Hamburg, Germany
  • 10Department of Neurology, Community Hospital Dr Horst Schmidt Klinikum Wiesbaden, Wiesbaden, Germany
  • 11Department of Neurology, Community Hospital Helios Klinikum Berlin-Buch, Berlin, Germany
  • 12Department of Neurology, Community Hospital Asklepios Klinik St Georg, Hamburg, Germany
  • 13Department of Neurology, Community Hospital Klinikum Stuttgart, Stuttgart, Germany
  • 14Department of Neurology, Community Hospital Klinikum Koblenz, Koblenz, Germany
  • 15Department of Neurology, Community Hospital Klinikum Dortmund, Dortmund, Germany
  • 16Department of Neurology, University of Würzburg, Würzburg, Germany
  • 17Institute of Clinical Epidemiology and Biometry, Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany
  • 18Department of Neurology, University of Leipzig, Leipzig, Germany
  • 19Department of Neurology, Community Hospital Bad Hersfeld, Bad Hersfeld, Germany
  • 20Department of Neurology, University of Dresden, Dresden, Germany
  • 21Department of Neurology, University of Cologne, Cologne, Germany
  • 22Department of Neurology, University of Jena, Jena, Germany
  • 23Department of Neurology, Community Hospital Fulda, Fulda, Germany
  • 24Department of Neurology, Community Hospital Nuremberg, Nuremberg, Germany
  • 25Department of Neuroradiology, University of Erlangen-Nuremberg, Erlangen, Germany
JAMA. 2015;313(8):824-836. doi:10.1001/jama.2015.0846

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