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Clinical Characteristics and Outcomes Associated With Oral Anticoagulant Use Among Patients Hospitalized With Intracerebral Hemorrhage

  • Xian, Ying1, 2
  • Zhang, Shuaiqi1
  • Inohara, Taku3, 4
  • Grau-Sepulveda, Maria1
  • Matsouaka, Roland A.1, 5
  • Peterson, Eric D.1
  • Piccini, Jonathan P.1
  • Smith, Eric E.6
  • Sheth, Kevin N.7
  • Bhatt, Deepak L.8
  • Fonarow, Gregg C.9
  • Schwamm, Lee H.10
  • 1 The Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina
  • 2 Department of Neurology, Duke University Medical Center, Durham, North Carolina
  • 3 Department of Cardiology, Keio University School of Medicine, Tokyo, Japan
  • 4 Division of Cardiology, Vancouver General Hospital, University of British Columbia, Vancouver, Canada
  • 5 Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina
  • 6 Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, Canada
  • 7 Department of Neurology, Yale School of Medicine, New Haven, Connecticut
  • 8 Brigham and Women’s Hospital Heart and Vascular Center, Harvard Medical School, Boston, Massachusetts
  • 9 Division of Cardiology, University of California at Los Angeles, Los Angeles
  • 10 Department of Neurology, Massachusetts General Hospital, Boston
Published Article
JAMA Network Open
American Medical Association
Publication Date
Feb 16, 2021
DOI: 10.1001/jamanetworkopen.2020.37438
PMID: 33591368
PMCID: PMC7887660
PubMed Central
  • Neurology
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Importance Although the use of factor Xa (FXa) inhibitors has increased substantially over the past decade, there are limited data on characteristics and outcomes of FXa inhibitor–associated intracerebral hemorrhage (ICH). Objective To investigate the association between prior oral anticoagulant use (FXa inhibitors, warfarin, or none) and in-hospital outcomes among patients with nontraumatic ICH. Design, Setting, and Participants This is a cohort study of 219 701 patients with nontraumatic ICH admitted to 1870 hospitals in the Get With The Guidelines–Stroke registry between October 2013 and May 2018. Data analysis was performed in December 2019. Exposures Anticoagulation therapy before ICH. Main Outcomes and Measures The primary outcome was in-hospital mortality. Secondary outcomes were a composite measure of in-hospital mortality or discharge to hospice, discharge home, independent ambulation, and modified Rankin Scale (mRS) score at discharge. Results Of 219 701 patients (mean [SD] age, 68.2 [15.3] years; 104 940 women [47.8%]), 9202 (4.2%) were taking FXa inhibitors, 21 430 (9.8%) were taking warfarin, and 189 069 (86.0%) were not taking any oral anticoagulant before ICH. Patients taking FXa inhibitors or warfarin were older and had higher prevalence of cardiovascular risk factors. Compared with those not taking an oral anticoagulant (42 660 of 189 069 patients [22.6%]), the in-hospital mortality risk was higher for both FXa inhibitors (2487 of 9202 patients [27.0%]; adjusted odds ratio [aOR], 1.27; 95% CI, 1.20-1.34; P < .001) and warfarin (7032 of 21 430 patients [32.8%]; aOR, 1.67; 95% CI, 1.60-1.74; P < .001). Both FXa inhibitors (3478 of 9202 patients [37.8%]; aOR, 1.19; 95% CI, 1.13-1.26; P < .001) and warfarin (9151 of 21 430 patients [42.7%]; aOR, 1.50; 95% CI, 1.44-1.56; P < .001) were associated with higher odds of death or discharge to hospice compared with not taking oral anticoagulation (58 022 of 189 069 patients [30.7%]). Although the rates of discharge home, independent ambulation, mRS scores of 0 or 1, and mRS scores of 0 to 2 were numerically lower among patients taking FXa inhibitors, these differences were not significant compared with patients not taking oral anticoagulants. In contrast, patients taking FXa inhibitors were less likely to die (aOR, 0.76; 95% CI, 0.72-0.81; P < .001) or to experience death or discharge to hospice (aOR, 0.79; 95% CI, 0.75-0.84; P < .001), more likely to be discharged home (aOR, 1.18; 95% CI, 1.10-1.26; P < .001), and had better mRS scores at discharge (eg, mRS scores of 0-1: aOR, 1.24; 95% CI, 1.09-1.40; P < .001) than those treated with warfarin. Concomitant warfarin and antiplatelet therapy (either single or dual) was associated with worse outcomes compared with taking warfarin alone (eg, in-hospital mortality for dual-antiplatelet agents: aOR, 2.07; 95% CI, 1.72-2.50; P < .001). However, such incremental risk was not significant in patients taking FXa inhibitors. Conclusions and Relevance In this cohort study, FXa inhibitor–associated ICH was associated with higher risk of mortality or death or discharge to hospice than not taking an oral anticoagulant, but patients taking FXa inhibitors had better outcomes than those with warfarin-related ICH.

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