Early versus Late initiation of direct oral Anticoagulants in post-ischaemic stroke patients with atrial fibrillatioN (ELAN): Protocol for an international, multicentre, randomised-controlled, two-arm, open, assessor-blinded trial

Fischer, U. et al. (2022) Early versus Late initiation of direct oral Anticoagulants in post-ischaemic stroke patients with atrial fibrillatioN (ELAN): Protocol for an international, multicentre, randomised-controlled, two-arm, open, assessor-blinded trial. European Stroke Journal, 7(4), pp. 487-495. (doi: 10.1177/23969873221106043)

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Abstract

Rationale: Direct oral anticoagulants (DOAC) are highly effective in preventing ischaemic strokes in people with atrial fibrillation (AF). However, it is unclear how soon they should be started after acute ischaemic stroke (AIS). Early initiation may reduce early risk of recurrence but might increase the risk of haemorrhagic complications. Aim: To estimate the safety and efficacy of early initiation of DOACs compared to late guideline-based initiation in people with AIS related to AF. Methods and design: An international, multicentre, randomised (1:1) controlled, two-arm, open, assessor-blinded trial is being conducted. Early treatment is defined as DOAC initiation within 48 h of a minor or moderate stroke, or at day 6–7 following major stroke. Late treatment is defined as DOAC initiation after day 3–4 following minor stroke, after day 6–7 following moderate stroke and after day 12–14 following major stroke. Severity of stroke is defined according to imaging assessment of infarct size. Sample size: ELAN will randomise 2000 participants 1:1 to early versus late initiation of DOACs. This assumes a risk difference of 0.5% favouring the early arm, allowing an upper limit of the 95% confidence interval up to 1.5% based on the Miettinen & Nurminen formula. Outcomes: The primary outcome is a composite of symptomatic intracranial haemorrhage, major extracranial bleeding, recurrent ischaemic stroke, systemic embolism or vascular death at 30 ± 3 days after randomisation. Secondary outcomes include the individual components of the primary outcome at 30 ± 3 and 90 ± 7 days and functional status at 90 ± 7 days. Discussion: ELAN will estimate whether there is a clinically important difference in safety and efficacy outcomes following early anticoagulation with a DOAC compared to late guideline-based treatment in neuroimaging-selected people with an AIS due to AF.

Item Type:Articles
Additional Information:Funding: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: ELAN is an investigator-initiated clinical trial. The sponsor of the trial is the University Hospital Bern (Inselspital) and the trial is supported by grants from the Swiss National Science Foundation (32003B_197009; 32003B_169975), the Swiss Heart Foundation, the UK Stroke Association (2017/02) and the Intramural Research Fund (20-4-5) for Cardiovascular Diseases of the National Cerebral and Cardiovascular Centre, Japan.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Dawson, Professor Jesse
Authors: Fischer, U., Trelle, S., Branca, M., Salanti, G., Paciaroni, M., Ferrari, C., Abend, S., Beyeler, S., Strbian, D., Thomalla, G., Ntaios, G., Bonati, L. H., Michel, P., Nedeltchev, K., Gattringer, T., Sandset, E. C., Kelly, P., Lemmens, R., Koga, M., Sylaja, P. N., de Sousa, D. A., Bornstein, N. M., Gdovinova, Z., Seiffge, D. J., Gralla, J., Horvath, T., Dawson, J., and on behalf of the ELAN Investigators,
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:European Stroke Journal
Publisher:SAGE Publications
ISSN:2396-9873
ISSN (Online):2396-9881
Published Online:15 June 2022

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