Once versus twice daily direct oral anticoagulants in patients with recent stroke and atrial fibrillation

Alexandros A Polymeris; Annaelle Zietz; Fabian Schaub; Louisa Meya; Christopher Traenka; Sebastian Thilemann; Benjamin Wagner; Lisa Hert; Valerian L Altersberger; David J Seiffge; Flurina Lyrer; Tolga Dittrich; Ines Piot; Josefin Kaufmann; Lea Barone; Ludvig Dahlheim; Sophie Flammer; Nikolaos S Avramiotis; Nils Peters; Gian Marco De Marchis; Leo H Bonati; Henrik Gensicke; Stefan T Engelter; Philippe A Lyrer

doi:10.1177/23969873221099477

Once versus twice daily direct oral anticoagulants in patients with recent stroke and atrial fibrillation

Eur Stroke J. 2022 Sep;7(3):221-229. doi: 10.1177/23969873221099477. Epub 2022 May 10.

Authors

Alexandros A Polymeris^{1

2}, Annaelle Zietz¹, Fabian Schaub¹, Louisa Meya^{1

2}, Christopher Traenka^{1

2}, Sebastian Thilemann¹, Benjamin Wagner¹, Lisa Hert³, Valerian L Altersberger¹, David J Seiffge⁴, Flurina Lyrer¹, Tolga Dittrich¹, Ines Piot^{1

2}, Josefin Kaufmann^{1

2}, Lea Barone^{1

2}, Ludvig Dahlheim⁵, Sophie Flammer⁵, Nikolaos S Avramiotis¹, Nils Peters^{1

2

6}, Gian Marco De Marchis¹, Leo H Bonati¹, Henrik Gensicke^{1

2}, Stefan T Engelter^{1

2}, Philippe A Lyrer¹

Affiliations

¹ Department of Neurology and Stroke Center, University Hospital Basel and University of Basel, Basel, Switzerland.
² Neurology and Neurorehabilitation, University Department of Geriatric Medicine Felix Platter, University of Basel, Basel, Switzerland.
³ Department of Intensive Care Medicine, University Hospital Basel and University of Basel, Basel, Switzerland.
⁴ Department of Neurology, Inselspital, University Hospital and University of Bern, Bern, Switzerland.
⁵ Medical Faculty, University of Basel, Basel, Switzerland.
⁶ Stroke Center, Klinik Hirslanden Zurich, Zurich, Switzerland.

Abstract

Background: Data on the safety and effectiveness of once-daily (QD) versus twice-daily (BID) direct oral anticoagulants (DOAC) in comparison to vitamin K antagonists (VKA) and to one another in patients with atrial fibrillation (AF) and recent stroke are scarce.

Patients and methods: Based on prospectively obtained data from the observational registry Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients(NOACISP)-LONGTERM (NCT03826927) from Basel, Switzerland, we compared the occurrence of the primary outcome - the composite of recurrent ischemic stroke, major bleeding, and all-cause death - among consecutive AF patients treated with either VKA, QD DOAC, or BID DOAC following a recent stroke using Cox proportional hazards regression including adjustment for potential confounders.

Results: We analyzed 956 patients (median age 80 years, 46% female), of whom 128 received VKA (13.4%), 264 QD DOAC (27.6%), and 564 BID DOAC (59%). Over a total follow-up of 1596 patient-years, both QD DOAC and BID DOAC showed a lower hazard for the composite outcome compared to VKA (adjusted HR [95% CI] 0.69 [0.48, 1.01] and 0.66 [0.47, 0.91], respectively). Upon direct comparison, the hazard for the composite outcome did not differ between patients treated with QD versus BID DOAC (adjusted HR [95% CI] 0.94 [0.70, 1.26]). Secondary analyses focusing on the individual components of the composite outcome revealed no clear differences in the risk-benefit profile of QD versus BID DOAC.

Discussion and conclusion: The overall benefit of DOAC over VKA seems to apply to both QD and BID DOAC in AF patients with a recent stroke, without clear evidence that one DOAC dosing regimen is more advantageous than the other.

Keywords: Direct oral anticoagulants; atrial fibrillation; once-daily; regimen; stroke; twice-daily.