J Stroke.
2025 May;27(2):217-227. 10.5853/jos.2024.04322.
Antiplatelet Use Prior to Anticoagulant Initiation in Patients With Atrial Fibrillation-Related Ischemic Stroke: An ELAN Trial Analysis
- Polymeris AA1,2
- Koga M3
- Strbian D4
- Vedamurthy A5
- Krishnan M6
- Branca M7
- Horvath T8
- Goeldlin M8
- Shim G9
- Gumbinger C10
- Zhang L11
- Kristoffersen ES12,13
- Desfontaines P14
- Vanacker P15
- Alonso A16
- Poli S17,18
- Nunes AP19
- Caracciolo NG20
- Kneihsl M21,22
- Kahles T23
- Giudici D24
- Räty S4
- Tiainen M4
- Dawson J25
- Fischer U
8 - the ELAN Investigators1
- Affiliations
-
- 1Department of Neurology and Stroke Center, University Hospital Basel and University of Basel, Basel, Switzerland
- 2Stroke Division, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
- 3Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan
- 4Department of Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
- 5Glan Clwyd Hospital, Betsi Cadwaladr University Local Health Board, Rhyl, UK
- 6Stroke Unit, Morriston Hospital, Swansea Bay University Health Board, Swansea, UK
- 7Department of Clinical Research, Clinical Trial Unit (CTU) Bern, University of Bern, Bern, Switzerland
- 8Department of Neurology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
- 9University Hospital of North Durham, Durham, UK
- 10Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany
- 11Department of Neurology, St George’s University Hospital, London, UK
- 12Department of Neurology, Akershus University Hospital, Lørenskog, Norway
- 13Department of General Practice, University of Oslo, Oslo, Norway
- 14Stroke Unit, Department of Neurology, CHC-Groupe Santé, Liège, Belgium
- 15Department of Neurology, AZ Groeninge, Kortrijk, Belgium
- 16Department of Neurology, University Medical Center Mannheim and Mannheim Center for Translational Neurosciences, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
- 17Department of Neurology & Stroke, Eberhard Karls University Tübingen, Tübingen, Germany
- 18Hertie Institute for Clinical Brain Research, Eberhard Karls University Tübingen, Tübingen, Germany
- 19Internal Medicine, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
- 20Department of Human Neurosciences, University La Sapienza, Rome, Italy
- 21Department of Neurology, Medical University of Graz, Graz, Austria
- 22Division of Neuroradiology, Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria
- 23Department of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland
- 24Internal, Vascular, and Emergency Medicine, Stroke Unit, Santa Maria della Misericordia Hospital, University of Perugia, Perugia, Italy
- 25School of Cardiovascular and Metabolic Health, College of Medical, Veterinary & Life Sciences, Queen Elizabeth University Hospital, Glasgow, UK
- KMID: 2568227
- DOI: http://doi.org/10.5853/jos.2024.04322
Abstract
- Background and Purpose
Antiplatelets are often used before direct oral anticoagulant (DOACs) initiation after an acute ischemic stroke related to atrial fibrillation (AF), but the evidence is weak. Here, we explored the risks and benefits of this approach.
Methods
A post-hoc analysis of ELAN (Early versus Late Initiation of Direct Oral Anticoagulants in Post-ischemic Stroke Patients with Atrial Fibrillation) trial data (NCT03148457) was conducted to compare the risk of recurrent ischemic stroke, systemic embolism, major bleeding (extracranial or intracranial hemorrhage [ICH]), and vascular death within 30 days (as a composite and as individual outcomes) in participants treated with and without antiplatelets before DOAC initiation after an AF-associated ischemic stroke. We used both logistic and cause-specific Cox proportional hazards regression in inverse probability of treatment weighted models to account for confounding. We calculated the net benefit of antiplatelet use by subtracting the weighted rate of excess bleeding events attributable to antiplatelets from the rate of excess ischemic events possibly prevented by antiplatelets.
Results
Among 2,013 participants (median age 77 years, 45.5% female), 1,090 (54.1%) used antiplatelets, and 70 (3.5%) experienced the composite outcome. Antiplatelet use was not associated with the composite outcome (inverse probability of treatment weighted odds ratio [ORweighted] 1.06, 95% confidence interval [CI] 0.66–1.72; inverse probability of treatment weighted hazard ratio [HRweighted] 1.06, 95% CI 0.65–1.72), but showed a lower risk of ischemic stroke recurrence (ORweighted 0.58 [0.30–1.08], HRweighted 0.57 [0.30–1.10]), and a higher risk of major bleeding (ORweighted 1.76 [0.56–6.63], HRweighted 1.88 [0.56–6.39]). Its net benefit was +0.57 (95% CI -1.25 to +2.34) to +0.30 (-1.82 to +2.27) weighted events/100 person-months for ICH weights 1.5 to 3.1.
Conclusion
Following an AF-associated ischemic stroke, we found a lower risk of recurrence and no signs of net harm with antiplatelet use before DOAC initiation, despite an increased risk of bleeding.
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