Volume and functional outcome of intracerebral hemorrhage according to oral anticoagulant type

Objective: To compare intracerebral hemorrhage (ICH) volume and clinical outcome of non–vitamin K oral anticoagulants (NOAC)–associated ICH to warfarin-associated ICH. Methods: In this multicenter cross-sectional observational study of patients with anticoagulant-associated ICH, consecutive patients with NOAC-ICH were compared to those with warfarin-ICH selected from a population of 344 patients with anticoagulant-associated ICH. ICH volume was measured by an observer blinded to clinical details. Outcome measures were ICH volume and clinical outcome adjusted for confounding factors. Results: We compared 11 patients with NOAC-ICH to 52 patients with warfarin-ICH. The median ICH volume was 2.4 mL (interquartile range [IQR] 0.3–5.4 mL) for NOAC-ICH vs 8.9 mL (IQR 4.0–21.3 mL) for warfarin-ICH (p = 0.0028). In univariate linear regression, use of warfarin (difference in cube root volume 1.61; 95% confidence interval [CI] 0.69 to 2.53) and lobar ICH location (compared with nonlobar ICH; difference in cube root volume 1.52; 95% CI 2.20 to 0.85) were associated with larger ICH volumes. In multivariable linear regression adjusting for confounding factors (sex, hypertension, previous ischemic stroke, white matter disease burden, and premorbid modified Rankin Scale score [mRS]), warfarin use remained independently associated with larger ICH (cube root) volumes (coefficient 0.64; 95% CI 0.24 to 1.25; p = 0.042). Ordered logistic regression showed an increased odds of a worse clinical outcome (as measured by discharge mRS) in warfarin-ICH compared with NOAC-ICH: odds ratio 4.46 (95% CI 1.10 to 18.14; p = 0.037). Conclusions: In this small prospective observational study, patients with NOAC-associated ICH had smaller ICH volumes and better clinical outcomes compared with warfarin-associated ICH.

[1]  H. Tomita,et al.  Characteristics of Intracerebral Hemorrhage During Rivaroxaban Treatment: Comparison With Those During Warfarin , 2014, Stroke.

[2]  D. Werring,et al.  Advances in understanding spontaneous intracerebral hemorrhage: insights from neuroimaging , 2014, Expert Review of Neurotherapeutics.

[3]  G. Hankey Intracranial Hemorrhage and Novel Anticoagulants for Atrial Fibrillation: What Have We Learned? , 2014, Current Cardiology Reports.

[4]  Alexander Parkhomenko,et al.  Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials , 2014, The Lancet.

[5]  Wei Zhou,et al.  Hemostatic Therapy in Experimental Intracerebral Hemorrhage Associated With Rivaroxaban , 2013, Stroke.

[6]  Y. Béjot,et al.  Intracerebral haemorrhage profiles are changing: results from the Dijon population-based study. , 2013, Brain : a journal of neurology.

[7]  K. Butcher,et al.  Poor Prognosis in Warfarin-Associated Intracranial Hemorrhage Despite Anticoagulation Reversal , 2012, Stroke.

[8]  D. Werring,et al.  Cerebral Microbleeds on Magnetic Resonance Imaging and Anticoagulant-Associated Intracerebral Hemorrhage Risk , 2012, Front. Neur..

[9]  S. Yusuf,et al.  Intracranial Hemorrhage in Atrial Fibrillation Patients During Anticoagulation With Warfarin or Dabigatran: The RE-LY Trial , 2012, Stroke.

[10]  S. Schulman,et al.  The Oral Thrombin Inhibitor Dabigatran: Strengths and Weaknesses , 2012, Seminars in Thrombosis & Hemostasis.

[11]  J. Ansell New oral anticoagulants should not be used as first-line agents to prevent thromboembolism in patients with atrial fibrillation. , 2012, Circulation.

[12]  S. Schwab,et al.  Semi‐automatic volumetric assessment of perihemorrhagic edema with computed tomography , 2011, European journal of neurology.

[13]  Flor A. Cianchetti,et al.  Anticoagulation With the Oral Direct Thrombin Inhibitor Dabigatran Does Not Enlarge Hematoma Volume in Experimental Intracerebral Hemorrhage , 2011, Circulation.

[14]  V. Laux,et al.  Rivaroxaban: A New Oral Factor Xa Inhibitor , 2010, Arteriosclerosis, thrombosis, and vascular biology.

[15]  Ale Algra,et al.  Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis , 2010, The Lancet Neurology.

[16]  P. Rothwell,et al.  Change in incidence and aetiology of intracerebral haemorrhage in Oxfordshire, UK, between 1981 and 2006: a population-based study , 2007, The Lancet Neurology.

[17]  A. Spyropoulos Investigational treatments of venous thromboembolism , 2007, Expert opinion on investigational drugs.

[18]  J. Broderick,et al.  The increasing incidence of anticoagulant-associated intracerebral hemorrhage , 2007, Neurology.

[19]  P. Scheltens,et al.  A New Rating Scale for Age-Related White Matter Changes Applicable to MRI and CT , 2001, Stroke.

[20]  S. Rapaport,et al.  Localization of human tissue factor antigen by immunostaining with monospecific, polyclonal anti-human tissue factor antibody. , 1990, Thrombosis research.

[21]  P. Sandercock,et al.  A prospective study of acute cerebrovascular disease in the community: the Oxfordshire Community Stroke Project--1981-86. 2. Incidence, case fatality rates and overall outcome at one year of cerebral infarction, primary intracerebral and subarachnoid haemorrhage. , 1990, Journal of neurology, neurosurgery, and psychiatry.

[22]  K. Mann,et al.  The kinetics of activation of normal and gamma-carboxyglutamic acid-deficient prothrombins. , 1985, The Journal of biological chemistry.

[23]  J. Jesty,et al.  Tissue factor-dependent activation of tritium-labeled factor IX and factor X in human plasma. , 1984, Blood.

[24]  R. Rosenberg,et al.  A spectrum of partially carboxylated prothrombins in the plasmas of coumarin-treated patients. , 1977, Biochimica et biophysica acta.