TY  - JOUR
A1  - Bieber, Michael
A1  - Foerster, Kathrin I.
A1  - Haefeli, Walter E.
A1  - Pham, Mirko
A1  - Schuhmann, Michael K.
A1  - Kraft, Peter
T1  - Treatment with edoxaban attenuates acute stroke severity in mice by reducing blood–brain barrier damage and inflammation
JF  - International Journal of Molecular Sciences
N2  - 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.
KW  - edoxaban
KW  - thrombo-inflammation
KW  - blood–brain barrier
KW  - tMCAO
KW  - experimental stroke
KW  - hemorrhagic transformation
KW  - NOAC
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284481
SN  - 1422-0067
VL  - 22
IS  - 18
ER  - 
TY  - JOUR
A1  - Tütüncü, Serdar
A1  - Olma, Manuel
A1  - Kunze, Claudia
A1  - Dietzel, Joanna
A1  - Schurig, Johannes
A1  - Fiessler, Cornelia
A1  - Malsch, Carolin
A1  - Haas, Tobias Eberhard
A1  - Dimitrijeski, Boris
A1  - Doehner, Wolfram
A1  - Hagemann, Georg
A1  - Hamilton, Frank
A1  - Honermann, Martin
A1  - Jungehulsing, Gerhard Jan
A1  - Kauert, Andreas
A1  - Koennecke, Hans-Christian
A1  - Mackert, Bruno-Marcel
A1  - Nabavi, Darius
A1  - Nolte, Christian H.
A1  - Reis, Joschua Mirko
A1  - Schmehl, Ingo
A1  - Sparenberg, Paul
A1  - Stingele, Robert
A1  - Völzke, Enrico
A1  - Waldschmidt, Carolin
A1  - Zeise-Wehry, Daniel
A1  - Heuschmann, Peter U.
A1  - Endress, Matthias
A1  - Haeusler, Karl Georg
T1  - Off-label-dosing of non-vitamin K-dependent oral antagonists in AF patients before and after stroke: results of the prospective multicenter Berlin Atrial Fibrillation Registry
JF  - Journal of Neurology
N2  - Aims
We aimed to analyze prevalence and predictors of NOAC off-label under-dosing in AF patients before and after the index stroke.
Methods
The post hoc analysis included 1080 patients of the investigator-initiated, multicenter prospective Berlin Atrial Fibrillation Registry, designed to analyze medical stroke prevention in AF patients after acute ischemic stroke.
Results
At stroke onset, an off-label daily dose was prescribed in 61 (25.5%) of 239 NOAC patients with known AF and CHA2DS2-VASc score ≥ 1, of which 52 (21.8%) patients were under-dosed. Under-dosing was associated with age ≥ 80 years in patients on rivaroxaban [OR 2.90, 95% CI 1.05-7.9, P = 0.04; n = 29] or apixaban [OR 3.24, 95% CI 1.04-10.1, P = 0.04; n = 22]. At hospital discharge after the index stroke, NOAC off-label dose on admission was continued in 30 (49.2%) of 61 patients. Overall, 79 (13.7%) of 708 patients prescribed a NOAC at hospital discharge received an off-label dose, of whom 75 (10.6%) patients were under-dosed. Rivaroxaban under-dosing at discharge was associated with age ≥ 80 years [OR 3.49, 95% CI 1.24-9.84, P = 0.02; n = 19]; apixaban under-dosing with body weight ≤ 60 kg [OR 0.06, 95% CI 0.01-0.47, P < 0.01; n = 56], CHA2DS2-VASc score [OR per point 1.47, 95% CI 1.08-2.00, P = 0.01], and HAS-BLED score [OR per point 1.91, 95% CI 1.28-2.84, P < 0.01].
Conclusion
At stroke onset, off-label dosing was present in one out of four, and under-dosing in one out of five NOAC patients. Under-dosing of rivaroxaban or apixaban was related to old age. In-hospital treatment after stroke reduced off-label NOAC dosing, but one out of ten NOAC patients was under-dosed at discharge.
KW  - NOAC
KW  - ischemic stroke
KW  - atrial fibrillation
KW  - under-dosing
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-266969
SN  - 1432-1459
VL  - 269
IS  - 1
ER  -