• Flemming Skjøth, Torben Bjerregaard Larsen, Alexander Rieem Dun, Mathias Lilja, Iffat Rahman, Khaled Abdelgawwad, Sigrun Halvorsen, Craig Coleman, and Marcela Rivera.
• Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark; Research Data and Biostatistics, Aalborg University Hospital, Aalborg, Denmark.
• Am. J. Med. 2024 Jun 1; 137 (6): 520528.e13520-528.e13.

BackgroundThis Nordic observational cohort study aims to assess the effectiveness and safety of reduced-dose direct-acting oral anticoagulants (DOACs) dabigatran, rivaroxaban, and apixaban compared to standard warfarin for stroke prevention in nonvalvular atrial fibrillation.MethodsThe study, utilizing nationwide administrative databases from Denmark, Sweden, Norway, and Finland, spanned from January 1, 2011 to December 31, 2018 (2017 for Sweden). The cohort included 26,883 patients initiating reduced-dose DOACs and 108,014 comparable warfarin patients. Effectiveness was measured by the composite endpoint of ischemic stroke and systemic embolism, while safety was assessed through intracranial hemorrhage.ResultsThe meta-analysis across countries revealed similar or lower incidences of ischemic stroke and systemic embolism in patients on reduced-dose DOACs compared to standard warfarin (rivaroxaban: HR 0.93, dabigatran: HR 0.88, apixaban: HR 0.79). Incidences within warfarin groups ranged from 2.16 to 3.71 per 100 person-years, comparable to DOAC recipients. Intracranial hemorrhage rates were generally low, ranging from 0.16 to 1.85 per 100 person-years. In comparison with warfarin patients, meta-analyses yielded HRs for rivaroxaban (1.41), dabigatran (0.35), and apixaban (0.72).ConclusionsIn this study, atrial fibrillation patients initiating reduced-dose rivaroxaban and dabigatran exhibited incidences of ischemic stroke and systemic embolism similar to warfarin, and for apixaban, even lower. Rates of intracranial hemorrhage were comparable to or lower for patients on DOACs compared to warfarin.Copyright © 2024 Elsevier Inc. All rights reserved.

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