Abstract
Patients with atrial fibrillation and previous ischemic stroke (IS) are at increased risk of cerebrovascular events despite anticoagulation. In these patients, treatment with non-vitamin K oral anticoagulants (NOAC) such as edoxaban reduced the probability and severity of further IS without increasing the risk of major bleeding. However, the detailed protective mechanism of edoxaban has not yet been investigated in a model of ischemia/reperfusion injury. Therefore, in the current study we aimed to assess in a clinically relevant setting whether treatment with edoxaban attenuates stroke severity, and whether edoxaban has an impact on the local cerebral inflammatory response and blood–brain barrier (BBB) function after experimental IS in mice. Focal cerebral ischemia was induced by transient middle cerebral artery occlusion in male mice receiving edoxaban, phenprocoumon or vehicle. Infarct volumes, functional outcome and the occurrence of intracerebral hemorrhage were assessed. BBB damage and the extent of local inflammatory response were determined. Treatment with edoxaban significantly reduced infarct volumes and improved neurological outcome and BBB function on day 1 and attenuated brain tissue inflammation. In summary, our study provides evidence that edoxaban might exert its protective effect in human IS by modulating different key steps of IS pathophysiology, but further studies are warranted.
Highlights
Patients with non-valvular atrial fibrillation (NVAF) are at increased risk of cerebrovascular events, especially if they have already suffered an ischemic stroke (IS) or a transient ischemic attack (TIA) [1]
In the current study we aimed to assess in a clinically relevant experimental model, whether treatment with edoxaban on one hand attenuates IS severity in context with low bleeding risk, and on the other hand has an impact on the local cerebral inflammatory response and blood–brain barrier (BBB) function after experimental IS in mice
Infarct volumes were significantly smaller in edoxaban-treated mice than in vehicleor phenprocoumon-treated mice (Figure 1B)
Summary
Patients with non-valvular atrial fibrillation (NVAF) are at increased risk of cerebrovascular events, especially if they have already suffered an ischemic stroke (IS) or a transient ischemic attack (TIA) [1]. In these patients, anticoagulation with vitamin K antagonists (VKA) reduced stroke risk by approximately 60% [2]. VKA act through an inhibition of vitamin K-dependent synthesis of coagulation factors in the liver Their use is complicated by drug–drug and drug–food interactions, the need for regular coagulation monitoring and because of the long half-life of VKA [2]. A reliable body of evidence shows that NOAC deliver at least the same protection as VKA in primary and secondary prevention of IS related to NVAF, with approximately half the risk of developing an intracranial hemorrhage (ICH) [3,4,5,6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
