title: Risk of long-term anticoagulation under sustained severe arterial hypertension: A translational study comparing warfarin and the new oral anticoagulant apixaban.
abstract: New oral anticoagulants for the prevention of stroke and systemic embolism in patients with atrial fibrillation have recently been introduced. In this translational study, we explored the risk of long-term anticoagulation on intracerebral hemorrhage under sustained severe arterial hypertension. We initiated anticoagulation with warfarin or apixaban in spontaneously hypertensive rats prone to develop severe hypertension and subsequent intracerebral bleeding complications. A non-anticoagulated group served as control. During an 11-week-study period, blood pressure, anticoagulation parameters, and clinical status were determined regularly. The incidence of histopathologically proven intracerebral hemorrhage was defined as the primary endpoint. Both warfarin and apixaban anticoagulation was fairly stable during the study period, and all rats developed severe hypertension. Intracerebral hemorrhage was determined in 29% (4/14) of warfarin rats and in 10% (1/10) of apixaban rats. Controls did not show cerebral bleeding complications (chi-square not significant). Mortality rate at study termination was 33% (2/6) in controls, 43% (6/14) in the warfarin group, and 60% (6/10) in the apixaban group. Animals died from extracerebral complications in most cases. Our study describes an experimental intracerebral hemorrhage model in the context of sustained hypertension and long-term anticoagulation. Extracerebral bleeding complications occurred more often in warfarin-treated animals compared with apixaban and control rats.
authors.affiliation: 1 Department of Neurology, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Waltraud
authors.initials: W
authors.lastname: Pfeilschifter
authors.affiliation: 1 Department of Neurology, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Thurid
authors.initials: T
authors.lastname: Steinstraesser
authors.affiliation: 2 Department of Anesthesiology and Operative Intensive Care Medicine, Kepler University Hospital, Linz, Austria.
authors.forename: Patrick
authors.initials: P
authors.lastname: Paulus
authors.affiliation: 1 Department of Neurology, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Pia Susan
authors.initials: PS
authors.lastname: Zeiner
authors.affiliation: 1 Department of Neurology, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Bohmann
authors.affiliation: 3 Zentrale Forschungseinheit, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Alf
authors.initials: A
authors.lastname: Theisen
authors.affiliation: 4 Department of Internal Medicine, Goethe-University, Frankfurt am Main, Germany.|5 CCB Coagulation Research Center, Bethanien Hospital, Frankfurt am Main, Germany.
authors.forename: Edelgard
authors.initials: E
authors.lastname: Lindhoff-Last
authors.affiliation: 6 Neurological Institute (Edinger Institute), Goethe-University, Frankfurt am Main, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Penski
authors.affiliation: 7 Institute of Neuroradiology, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Marlies
authors.initials: M
authors.lastname: Wagner
authors.affiliation: 6 Neurological Institute (Edinger Institute), Goethe-University, Frankfurt am Main, Germany.
authors.forename: Michel
authors.initials: M
authors.lastname: Mittelbronn
authors.affiliation: 1 Department of Neurology, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Foerch
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000401:mortality; D006470:Hemorrhage / Q000139:chemically induced / Q000401:mortality; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use; D011728:Pyridones / Q000009:adverse effects / Q000627:therapeutic use; D051381:Rats; D013997:Time Factors; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D014859:Warfarin
keywords: Antithrombotics; animal model; brain ischemia; hypertension; intracerebral hemorrhage