| Title: |
Once- versus twice-daily direct oral anticoagulants after ischemic stroke in atrial fibrillation - A post-hoc analysis of the ELAN trial |
| Authors: |
ELAN Investigators; 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 |
| Contributors: |
Neurologian yksikkö; Clinicum; HUS Neurocenter |
| Publisher Information: |
SAGE Publications Inc. |
| Publication Year: |
2025 |
| Collection: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| Subject Terms: |
Direct oral anticoagulants; Atrial fibrillation; Ischemic stroke; Once-daily; Regimen; Twice-daily; Neurology and psychiatry; General medicine; internal medicine and other clinical medicine |
| 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. ; Peer reviewed |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: ELAN was supported by the Swiss National Science Foundation (SNSF; 32003B_197009; 32003B_169975), the Swiss Heart Foundation (SHF), the Stroke Association in the United Kingdom (2017/02), and the Intramural Research Fund (20-4-5) for Cardiovascular Diseases of the National Cerebral and Cardiovascular Center, Japan. This work was supported in part by the 2024 Maupertuis Research Prize, awarded to Prof. Dr. med. Urs Fischer by the Swiss Brain League.; https://hdl.handle.net/10138/600267; 105013592564; 001546754300001 |
| Availability: |
https://hdl.handle.net/10138/600267 |
| Rights: |
cc_by ; info:eu-repo/semantics/openAccess ; openAccess |
| Accession Number: |
edsbas.770BA8FB |
| Database: |
BASE |