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Once- versus twice-daily direct oral anticoagulants after ischemic stroke in atrial fibrillation - A post-hoc analysis of the ELAN trial

Title: Once- versus twice-daily direct oral anticoagulants after ischemic stroke in atrial fibrillation - A post-hoc analysis of the ELAN trial
Authors: Polymeris, Alexandros A.; Rossel, Jean-Benoit; Koga, Masatoshi; Strbian, Daniel; Vedamurthy, Adhiyaman; Krishnan, Manju; Branca, Mattia; Meinel, Thomas; Kristoffersen, Espen Saxhaug; Yoshimoto, Takeshi; Tanaka, Kanta; Kunieda, Takenobu; Yakushiji, Yusuke; Vehoff, Jochen; Matsuzono, Kosuke; Slade, Peter; Demeestere, Jelle; Salerno, Alexander; Caracciolo, Nicoletta G.; Hemelsoet, Dimitri; Engelter, Stefan T.; Auer, Elias; Horvath, Thomas; Seiffge, David J.; Goeldlin, Martina; Dawson, Jesse; Fischer, Urs; ELAN, Investigators
Source: ISSN:2396-9873 ; ISSN:2396-9881 ; European Stroke Journal.
Publisher Information: SAGE Publications
Publication Year: 2025
Subject Terms: Science & Technology; Life Sciences & Biomedicine; Clinical Neurology; Peripheral Vascular Disease; Neurosciences & Neurology; Cardiovascular System & Cardiology; Direct oral anticoagulants; once-daily; twice-daily; regimen; ischemic stroke; atrial fibrillation; NET CLINICAL BENEFIT; RIVAROXABAN; PREVENTION; DABIGATRAN; MEDICATION; WARFARIN; EVENTS; PEOPLE; ATTACK; RISKS; ELAN Investigators; 3201 Cardiovascular medicine and haematology; 4202 Epidemiology; 4206 Public health
Description: INTRODUCTION: Whether the risk-benefit profile of once-daily versus twice-daily direct oral anticoagulants (DOAC) differs after atrial fibrillation(AF)-associated ischemic stroke is unclear. We explored this in a post-hoc analysis of ELAN trial data (NCT03148457). PATIENTS AND METHODS: We compared the risk of the primary outcome (recurrent ischemic stroke, systemic embolism, intracranial hemorrhage (ICH), major extracranial bleeding, vascular death) from treatment initiation to the trial's 90-day follow-up in participants treated with once-daily or twice-daily DOAC after AF-associated stroke using Firth's logistic and Cox proportional hazards regression in unadjusted, inverse-probability-of-treatment-weighted and augmented-inverse-probability-weighted models to address confounding. Secondary outcomes were the primary outcome components and non-major bleeding. We calculated the net clinical benefit (NCB) of twice-daily over once-daily DOAC by subtracting the weighted rate of excess bleeding attributable to twice-daily DOAC from the rate of excess ischemic events possibly prevented by twice-daily DOAC. RESULTS: We analyzed 1890/2013 (94%) participants (median age 77 years, 45% female), of whom 384 (20%) received once-daily and 1506 (80%) twice-daily DOAC. The primary outcome occurred in 64 (3.4%) participants, and did not differ between DOAC types in logistic (ORunadjusted 0.89 (95% CI 0.50-1.66); ORweighted 1.34 (0.71-2.79); ORaugmented 1.45 (0.81-3.21); twice-daily vs once-daily DOAC) nor in Cox models. We identified no clear differences in any secondary outcome. NCB analysis revealed a near-neutral net effect of twice-daily versus once-daily DOAC (+0.28 to +0.67 weighted events possibly prevented/100 person-months for ICH weights 1.5-3.3). DISCUSSION AND CONCLUSION: The risk-benefit profile of once-daily versus twice-daily DOAC after AF-associated ischemic stroke does not seem to differ. ; sponsorship: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or ...
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Relation: https://lirias.kuleuven.be/handle/20.500.12942/772458; https://doi.org/10.1177/23969873251360974; https://pubmed.ncbi.nlm.nih.gov/40785636
DOI: 10.1177/23969873251360974
Availability: https://lirias.kuleuven.be/handle/20.500.12942/772458; https://hdl.handle.net/20.500.12942/772458; https://lirias.kuleuven.be/retrieve/6ad0d682-e2d1-4620-bc79-a7119fa26850; https://doi.org/10.1177/23969873251360974; https://pubmed.ncbi.nlm.nih.gov/40785636
Rights: info:eu-repo/semantics/openAccess ; public ; https://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.73ED2A14
Database: BASE