Direct Oral Anticoagulant vs. Vitamin K Antagonist-Related Non-traumatic Intracerebral Hemorrhage
The Article: Tsivgoulis G, et al. Direct oral anticoagulant – vs vitamin K antagonist-related nontraumatic intracerebral hemorrhage. Neurology. 2017; 89: 1-10.
The Idea: Direct oral anticoagulants (DOACs) are used for prevention and treatment of venous thromboembolism. A feared complication of their use is severe hemorrhage, particularly intracranial hemorrhage. Multiple studies have found that there is a decreased incidence of intracerebral hemorrhage (ICH) with DOACs compared to vitamin K antagonists (VKAs); however, a study by Purucker in 2016 showed high risk for hematoma expansion and worse outcomes of ICH associated with DOACs. Also, the complication of DOAC-related ICH is concerning because there are no specific antidotes for these oral anticoagulants. The purpose of this study was to compare neuroimaging profiles and clinical outcomes between DOAC- and VKA-related ICH.
The Study: This is a prospective, multicenter, cross-sectional study that includes 13 international sites. The study enrolled consecutive patients with non-traumatic ICH and history of anticoagulant use presenting to the emergency departments of participating tertiary care stroke centers during a 1-year period from June 2015 to July 2016. A head CT scan was performed at baseline and again within 24 hours for each case. Neuroimaging parameters, such as hematoma volume and expansion, and clinical outcomes, such as modified Rankin Scale and NIH Stroke Scale scores were determined for each patient. Since data is limited, a systematic review and meta-analysis were also performed using available literature from 3 eligible studies to further evaluate associations of DOAC- vs. VKA-related ICH and radiologic and clinical outcomes.
The Findings: In the prospective study, 161 patients with ICH were included. 47 cases of ICH were DOAC-related and 114 were VKA-related. There was no difference in baseline demographics between the two groups except for a higher prevalence of chronic kidney disease in VKA-related ICH. Patients with DOAC-related ICH had lower median NIHSS scores (8 vs. 15), higher median GCS (14 vs 13), lower ICH volume, and lower ICH score, (an indicator of 30-day mortality) at presentation. Pharmacologic interventions, such as FFP, PCC, and vitamin K were more common in VKA-related ICH. There were no differences in the rates of invasive procedures performed in each group (defined as intubation, surgical decompression, or external ventricular drainage). Edema and midline shift were less prevalent on repeat neuroimaging at 24 hours for DOAC-related ICH. Patients with DOAC-related ICH had lower NIH Stroke Scale scores at 24 hours and lower modified Rankin Scale scores at discharge and at 3 months. When prospective data was analyzed in conjunction with data from the meta-analysis, lower in-hospital mortality rates and a trend towards lower rates of hematoma expansion were associated with the DOAC-related ICH group.
The Takeaway: Direct oral anticoagulant-related intracerebral hemorrhages appear to be overall less severe compared to vitamin K antagonist-related intracerebral hemorrhages in terms of neuroimaging profiles and clinical outcomes.