Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Sep;7(3):221-229.
doi: 10.1177/23969873221099477. Epub 2022 May 10.

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

Alexandros A Polymeris  1   2 , Annaelle Zietz  1 , Fabian Schaub  1 , Louisa Meya  1   2 , Christopher Traenka  1   2 , Sebastian Thilemann  1 , Benjamin Wagner  1 , Lisa Hert  3 , Valerian L Altersberger  1 , David J Seiffge  4 , Flurina Lyrer  1 , Tolga Dittrich  1 , Ines Piot  1   2 , Josefin Kaufmann  1   2 , Lea Barone  1   2 , Ludvig Dahlheim  5 , Sophie Flammer  5 , Nikolaos S Avramiotis  1 , Nils Peters  1   2   6 , Gian Marco De Marchis  1 , Leo H Bonati  1 , Henrik Gensicke  1   2 , Stefan T Engelter  1   2 , Philippe A Lyrer  1
Affiliations

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

Alexandros A Polymeris et al. Eur Stroke J. 2022 Sep.

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.

PubMed Disclaimer

Conflict of interest statement

Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AP: research support from the Swiss Academy of Medical Sciences/Bangerter-Rhyner Foundation and the Swiss Heart Foundation; CT: travel honoraria from Bayer; research support from the Swiss Heart Foundation, Freiwillige Akademische Gesellschaft Basel, Bangerter-Rhyner Foundation, University of Basel, Novartis Foundation for Medical and Biological Research; ST: travel grants from BMS/Pfizer; DJS: research support from the Science Funds and Stroke Funds University Hospital Basel, Swiss National Science Foundation, Swiss Society of Neurology, Bangerter-Rhyner Foundation, Daiichi-Sankyo; Thrombosis research prize from Bayer Foundation; compensation for educational efforts from Stago; advisory board fees from Portola/Alexion, Bayer, Pfizer; NP: research support from the Swiss National Science Foundation, Swiss Heart Foundation; advisory boards for AstraZeneca and Daiichi-Sankyo; speaker honoraria from Vifor and OMPharma Suisse; GMDM: support from the Swiss National Science Foundation; Spezialprogramm Nachwuchsförderung Klinische Forschung, University of Basel; Science Funds (Wissenschaftspool) University Hospital Basel; Swiss Heart Foundation; ProPatient Foundation Basel; Bangerter-Rhyner-Stiftung; Swisslife Jubiläumsstiftung for Medical Research; Swiss Neurological Society; Fondazione Dr Ettore Balli; De Quervain research grant; Thermo Fisher GmbH; travel honoraria by Bayer and BMS/Pfizer; speaker honoraria by Bayer and Medtronic; consultant honoraria by Bayer and Novartis; member of the Steering Committee of PACIFIC Stroke; Industry payments are made to the research fund of the University Hospital Basel; LHB: research support from the Swiss Heart Foundation, Swiss National Science Foundation, Stiftung zur Förderung der gastroenterologischen und allgemeinen klinischen Forschung sowie der medizinischen Bildauswertung; unrestricted research grant from AstraZeneca, personal fees from Amgen, Claret Medical, InnovHeart; HG: research support from the Swiss National Science Foundation; advisory board honoraria from Daiichi-Sankyo; funding for travel from BMS/Pfizer and AbbVie; STE: research support from the Swiss National Science Foundation, Swiss Heart Foundation, Freiwillige Akademische Gesellschaft Basel, Science Fund Rehabilitation, Felix Platter Basel, the Stroke Fund and Scientific Fund of the University Hospital Basel, Pfizer, Daiichi-Sankyo; compensation from Stago for educational material; travel or speaker honoraria from Bayer, Boehringer-Ingelheim, BMS, Daiichi-Sankyo; advisory boards for Bayer, Boehringer-Ingelheim, BMS; PAL: research support from the Swiss National Science Foundation, Swiss Heart Foundation, Research Funds Neurology University Hospital Basel; advisory board compensation from Boehringer-Ingelheim, Bayer, Recordati SA, Daiichi-Sankyo; travel support from Pfizer. The remaining authors declare no relevant conflicts.

Figures

Figure 1.
Figure 1.
Kaplan-Meier curves for the primary (composite) outcome according to type of oral anticoagulant.
Figure 2.
Figure 2.
Adjusted hazard ratio estimates for the effect of oral anticoagulant type on the primary composite outcome and all its individual components, (a) from models including both DOAC types and VKA as reference and (b) from models including only DOAC (with QD DOAC as reference).
See this image and copyright information in PMC

References

    1. No Authors. Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke. EAFT (European Atrial Fibrillation Trial) study group. Lancet 1993; 342: 1255–1262. - PubMed
    1. Ruff CT, Giugliano RP, Braunwald E, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014; 383: 955–962. - PubMed
    1. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): the Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J 2021; 42: 373–498. - PubMed
    1. Klijn CJ, Paciaroni M, Berge E, et al. Antithrombotic treatment for secondary prevention of stroke and other thromboembolic events in patients with stroke or transient ischemic attack and non-valvular atrial fibrillation: a European Stroke Organisation guideline. Eur Stroke J 2019; 4: 198–223. - PMC - PubMed
    1. Seiffge DJ, Paciaroni M, Wilson D, et al. Direct oral anticoagulants versus vitamin K antagonists after recent ischemic stroke in patients with atrial fibrillation. Ann Neurol 2019; 85: 823–834. - PMC - PubMed