The Great Terror of Oral Anticoagulant Use: Intracerebral hemorrhage

I am pleased to summarize a recent paper published by Dr. Xian on the clinical characteristics and outcomes associated with oral anticoagulants (OAC) use among patients hospitalized with intracerebral hemorrhage (ICH)1.

Major question addressed in the paper: 

What is the association between prior oral anticoagulant use (FXa inhibitor, Warfarin or none) and in-hospital outcomes among patients with nontraumatic ICH?


The investigators used the American Heart Association Stroke Association Get with The Guidelines-Stroke (GWTG-Stroke) registry to evaluate patients between October 2013 and May 2018, that had experience non-traumatic ICH with preceding use of FXa inhibitor compared with warfarin or none.  Patients with subarachnoid hemorrhage, subdural hematoma, or taking dabigatran were excluded. Included patients were defined by documentation ICH and use for at least 7 days of OAC, in three different groups: FXa inhibitor (rivaroxaban, apixaban, edoxaban); warfarin, or no use of OAC prior to hospital arrival and ICH.

Main outcomes and measures:

  • Primary outcome: In-hospital mortality
  • Secondary outcome: Composite of in-hospital mortality or discharge to hospice, discharge home, independent ambulation, and modified Rankin Scale (mRS) score at discharge.



  • Of 219,701 patients in the study, 104,940 were women (47.8%), 189,069 were not taking any OAC prior to ICH (86%), 9202 were taking FXa Inhibitors (4.2%), and 21,430 (9.8%) were taking warfarin.
  • One third of patients were taking concomitant antiplatelet therapy. This was more prevalent amongst patients taking FXa inhibitor (27%) and warfarin (30.1%) than those without taking OAC (24.8%).
  • NIHSS median score was 9 amongst the three groups. Patients taking warfarin had a higher mean NIHSS (12.5 {SD:11.3}).

Major results

  • FXa inhibitors (aOR: 1.27; p<0.001) and warfarin (aOR: 1.67; p<0.001) were associated with greater odds of in-hospital mortality compared with no OAC.
  • FXa inhibitors (aOR: 1.19; p<0.001) and warfarin (aOR: 1.50; p<0.001) were associated with greater odds of death or discharge to hospice compared with no OAC.
  • Patients with FXa were less likely to die (aOR 0.76; p<0.001) or be discharged to hospice (0.79; p<0.001) compared to those taking Warfarin.
  • Patients taking FXa were more likely to be discharged at home (aOR1.18; p<0.001) and have better mRS scores at discharge (aOR 1.24; p<0.001).
  • No statistical difference was found amongst the three groups regarding rates of discharge home, independent ambulation, or mRS score.
  • The use of single or dual antiplatelet, in patients taking warfarin was associated with higher odds of in-hospital mortality (aOR 2.07; p<0.001), and dead or discharge to hospice (aOR 1.86; p<0.001).

Major study limitations:

  1. The use of OAC use was defined as patients taking them 7 days prior to ICH, however the timing of the last doses of the OAC was not document, and it is possible that some patients might have not taken it or received a lower dose.
  2. Data regarding platelet transfusion was not recorded on the registry, and this might have influenced outcomes.

Key take-home message:

One of the most devastating complications of the use of FXa inhibitors is ICH, and although its prevalence is low (<0.5%), the in-hospital mortality can be as high as 27% as it was found on this study.  Although its high, when compared with prior use of warfarin, taking FXa inhibitors has a lower risk of mortality and dead or discharge to a hospice in the setting of ICH.

Potential future research:

  • Develop prospective studies that compare the available treatments for spontaneous ICH bleeding, four-factor prothrombin complexes concentrate vs. reverse factor Xa inhibitors (Andexanet). An underpowered retrospective study by Ammar et. Al,2 found no difference between these treatments due to the low number of patients analyzed in this study. Due to the burden of this complication we must find the most adequate treatment for non-traumatic ICH in the setting of FXa inhibitor use.



  1. Xian Y, Zhang S, Inohara T, et al. Clinical Characteristics and Outcomes Associated With Oral Anticoagulant Use Among Patients Hospitalized With Intracerebral Hemorrhage. JAMA Network Open. 2021;4(2):e2037438-e2037438.
  2. Ammar AA, Ammar MA, Owusu KA, et al. Andexanet Alfa Versus 4-Factor Prothrombin Complex Concentrate for Reversal of Factor Xa Inhibitors in Intracranial Hemorrhage. Neurocrit Care. 2021.

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”