What are the findings and implications of the ELAN (Evaluating New Therapies) trial?

The ELAN Trial: Findings and Implications

The ELAN (Early Versus Late Initiation of Direct Oral Anticoagulants) trial demonstrates that early initiation of direct oral anticoagulants after ischemic stroke in patients with atrial fibrillation does not significantly increase risk of adverse outcomes compared to late initiation, except in patients with parenchymal hemorrhage who may experience worse functional outcomes with early treatment. 1

Overview of the ELAN Trial

The ELAN trial was a randomized controlled trial investigating the optimal timing for initiating direct oral anticoagulants (DOACs) in patients who experienced an ischemic stroke and had atrial fibrillation. This is a critical clinical question as these patients face competing risks:

• Early risk: Hemorrhagic transformation of the stroke if anticoagulation is started too early
• Late risk: Recurrent ischemic stroke if anticoagulation is delayed too long

Key Findings

Primary Outcomes

• The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, major extracranial bleeding, systemic embolism, or vascular death within 30 days
• No significant difference was found between early versus late initiation of DOACs in the overall study population 1

Hemorrhagic Transformation Subgroup Analysis

• 12.5% of participants (247 of 1970) had hemorrhagic transformation (HT) on pre-randomization imaging
• For patients with HT, the adjusted risk difference between early versus late treatment was -2.2% (95% CI, -7.8% to 3.5%) 1
• For patients without HT, the adjusted risk difference was -0.9% (95% CI, -2.6% to 0.8%) 1

Functional Outcomes

• Important finding: Patients with parenchymal hemorrhage (PH) who received early treatment had worse 90-day functional outcomes with an adjusted risk difference of 25.1% (95% CI, 0.2% to 50.0%) for poor functional outcome (modified Rankin Scale score 3-6) 1
• No significant difference in functional outcomes for patients with hemorrhagic infarction or those without hemorrhagic transformation

Clinical Implications

1. General approach: Early initiation of DOACs after ischemic stroke in patients with atrial fibrillation appears to be safe for most patients

2. Caution needed: Patients with parenchymal hemorrhage on initial imaging may benefit from delayed anticoagulation due to potential for worse functional outcomes with early treatment

3. Individualized timing: The findings support a stratified approach to anticoagulation timing based on imaging findings:

   • Patients without hemorrhagic transformation: Consider early initiation
   • Patients with hemorrhagic infarction: Consider early initiation
   • Patients with parenchymal hemorrhage: Consider delayed initiation

Limitations and Considerations

• The ELAN trial was a single study, and results should be interpreted in the context of other evidence
• The findings specifically apply to DOACs and may not be generalizable to other anticoagulants
• Imaging assessment of hemorrhagic transformation was performed by a core laboratory, which may differ from real-world clinical practice

Conclusion

The ELAN trial provides important evidence regarding the timing of anticoagulation after ischemic stroke in patients with atrial fibrillation. While early initiation appears generally safe, patients with parenchymal hemorrhage may benefit from delayed anticoagulation to optimize functional outcomes.