Ischemic stroke and dose adjustment of oral Factor Xa inhibitors in patients with atrial fibrillation

• Published in: Journal of neurology 2020-07, Vol.267 (7), p.2007-2012
• Main Authors: Stoll, Svenja, Macha, Kosmas, Marsch, Armin, Gerner, Stefan T., Siedler, Gabriela, Fröhlich, Kilian, Volbers, Bastian, Strasser, Erwin F., Schwab, Stefan, Kallmünzer, Bernd
• Format: Article
• Language: English
• Subjects: Administration, Oral; Aged; Aged, 80 and over; Atrial Fibrillation - complications; Atrial Fibrillation - drug therapy; Cardiac arrhythmia; Diabetes mellitus; Factor Xa Inhibitors - administration & dosage; Factor Xa Inhibitors - blood; Female; Fibrillation; Follow-Up Studies; Guideline Adherence - standards; Humans; Ischemia; Ischemic Stroke - etiology; Ischemic Stroke - prevention & control; Labeling; Male; Medicine; Medicine & Public Health; Neurology; Neuroradiology; Neurosciences; Original Communication; Outcome Assessment, Health Care; Patients; Plasma levels; Practice Guidelines as Topic - standards; Registries; Severity of Illness Index; Sex Factors; Stroke
• ISSN: 0340-5354; 1432-1459
• DOI: 10.1007/s00415-020-09795-3

Background Oral Factor Xa inhibitors for the prevention of stroke in atrial fibrillation require dose adjustment based on certain clinical criteria, but the off-label use of the reduced doses is common. Methods Data from an observational registry including patients admitted with acute cerebral ischemia while taking oral Factor Xa inhibitors for atrial fibrillation between April 2016 and December 2018 were investigated. The dose regimen of the Xa inhibitor was classified as “appropriate”, “underdosed” and “overdosed” in conformity with the European Medicines Agency labelling. The effect of underdosing on the functional factor Xa plasma level on admission, the clinical stroke severity and the functional outcome after 3 months were investigated. Results 254 patients with cerebral ischemia while on Factor Xa inhibitors were included. The dose regimen of the Factor Xa inhibitor was appropriate in 166 patients (65%), underdosed in 67 patients (26%) and overdosed in 21 patients (8%). Underdosing was associated with female sex, diabetes mellitus and higher CHA 2 DS 2 –Vasc scores. Underdosing independently predicted lower anti-Xa plasma levels on admission [median 69.4 ng/ml (IQR 0.0–121.6) vs. 129.2 ng/ml (65.5–207.2); p