ELAN Trial: Early versus Later Anticoagulation for Stroke with Atrial Fibrillation
In patients with acute ischemic stroke and atrial fibrillation, does early DOAC initiation (within 48 hours for minor to moderate stroke) result in fewer recurrent events, hemorrhagic transformations, or deaths at 30 days compared with later initiation using the 1-3-6-12 day rule?
Fischer U, et al. N Engl J Med. 2023;388(26):2411-2421 · doi:10.1056/NEJMoa2303048 · 2,013 patients
Population
Included
- Age 18 years or older
- Acute ischemic stroke with confirmed atrial fibrillation (permanent, persistent, or paroxysmal)
- Imaging-based stroke severity classification: minor (small infarct, NIHSS 0-5), moderate (NIHSS 6-15, non-cortical dominant or non-large infarct), or major (NIHSS 16 or higher, or large cortical/hemispheric infarct)
- Planned DOAC anticoagulation for secondary prevention
- Randomization within 48 hours for minor or moderate stroke; within 6 to 24 hours for major stroke
- Acute ischemic stroke, defined as evidence of acute cerebral infarction on magnetic resonance imaging (MRI) or computed tomography (CT), or a clinical diagnosis of ischemic stroke with symptoms lasting more than 24 hours, confirmed by an investigator on the basis of a CT or MRI scan that excluded other causes
- Permanent, persistent, or paroxysmal nonvalvular atrial fibrillation, or atrial fibrillation diagnosed during hospitalization for the stroke
- Infarct size classified by the site investigators using a standardized visual rating scheme: minor (an infarct 1.5 cm or smaller), moderate (an infarct in the distribution of a cortical superficial branch of the middle, anterior, or posterior cerebral artery), or major (larger infarcts in those arterial distributions, or a brain-stem or cerebellar infarct larger than 1.5 cm)
- Able to be randomly assigned within 48 hours after a minor or moderate stroke, or within 6 to 24 hours after a major stroke
- Eligible for treatment with a direct oral anticoagulant (DOAC) for secondary prevention
- Written informed consent provided by the participant, next of kin, another legal representative, or an independent physician according to country-specific requirements
Excluded
- Hemorrhagic transformation on baseline imaging (symptomatic)
- Very large infarct with high hemorrhagic transformation risk at the treating clinician's discretion
- Prior stroke within 3 months
- Contraindication to anticoagulation (active bleeding, severe thrombocytopenia)
- Mechanical prosthetic heart valve (requires warfarin)
- Severe renal impairment precluding DOAC use
- Confluent parenchymal hematoma within the infarcted brain tissue, or intracranial hemorrhage remote from the infarcted tissue (petechial hemorrhage within infarcted tissue was not an exclusion)
- A requirement for therapeutic anticoagulation at stroke onset, with the exception of prophylactic low-molecular-weight heparin for the prevention of venous thromboembolism
- A mechanical prosthetic heart valve or another condition mandating a vitamin K antagonist rather than a DOAC
- Other detailed eligibility criteria specified in the trial protocol
Source: Fischer U et al., New England Journal of Medicine 2023;388(26):2411-2421· Retrieved 2026-06-09
Primary Outcome
Negligible absolute difference
Event-free at 30 Days (complement of composite)
Study Arms
- Agent
- Any direct oral anticoagulant (DOAC) with marketing authorization for the prevention of stroke and systemic embolism in the trial-site country, given at the appropriate dose
- Dose
- Appropriate label dose of the chosen DOAC (details of the specific DOACs and doses reported in the trial Supplementary Appendix)
- Route
- Oral
- Frequency
- Per the standard once-daily or twice-daily schedule of the selected DOAC
- Duration
- Continued for secondary prevention; trial follow-up to 90 days
- Co-interventions
- Participants in both groups continued to receive stroke care according to local standards. Intravenous thrombolysis or thrombectomy before randomization was permitted.
Early treatment was defined as initiation of a DOAC within 48 hours after a minor or moderate stroke, and on day 6 or 7 after a major stroke. Definitions verbatim from Fischer NEJM 2023 p.2413 (Trial Treatment). Estimation design: no formal noninferiority or superiority hypothesis was tested; the trial produced a point estimate and confidence interval for the between-group difference. ClinicalTrials.gov NCT03148457.
- Agent
- The same range of approved DOACs, started later according to the guideline-based 1-3-6-12 day rule
- Dose
- Appropriate label dose of the chosen DOAC (same options as the early group)
- Route
- Oral
- Frequency
- Per the standard once-daily or twice-daily schedule of the selected DOAC
- Duration
- Continued for secondary prevention; trial follow-up to 90 days
- Co-interventions
- Stroke care according to local standards in both groups, including thrombolysis or thrombectomy before randomization when used.
Later treatment was defined as initiation of a DOAC on day 3 or 4 after a minor stroke, on day 6 or 7 after a moderate stroke, and on day 12, 13, or 14 after a major stroke (the imaging-severity-based "1-3-6-12 day rule"). Definitions verbatim from Fischer NEJM 2023 p.2413 (Trial Treatment).
Trial Design
Type
- International, multicenter, open-label, assessor-blinded trial
- 1:1 randomization to early vs later DOAC initiation
- Imaging-based stroke severity classification (minor/moderate/major)
Timeline
Enrolled Nov 2017 – Sep 2022, 103 sites, 15 countries
N
2,013
Enrollment
2,013 patients across 103 sites in 15 countries. Enrolled Nov 2017 to Sep 2022.
ClinicalTrials.gov
NCT03148457Bedside Pearl
ELAN showed sICH 0.2% in both groups, recurrent ischemic stroke 1.4% (early) vs 2.5% (later). The trial supports early DOAC in AF stroke when imaging allows it. The risk difference upper bound of +0.47pp means early treatment could be at most marginally worse than delayed, not substantially more dangerous.
See also