Early Versus Late Initiation of Direct Oral Anticoagulants in Postischemic Stroke Patients With Atrial Fibrillation - ELAN

Jun 17, 2024
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Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Summary Reviewer:
Kim A. Eagle, MD, MACC
Date Published:
05/16/2024
Date Updated:
06/17/2024
Original Posted Date:
06/29/2023
References

Contribution To Literature:

Highlighted text has been updated as of June 17, 2024.

The ELAN trial showed possible benefit of early anticoagulation compared with delayed anticoagulation after acute ischemic stroke and AF.

Description:

The goal of the ELAN trial was to evaluate early anticoagulation compared with delayed anticoagulation among patients with acute ischemic stroke and atrial fibrillation (AF).

Study Design

  • Randomized
  • Parallel
  • Open-label

Patients with acute ischemic stroke and AF were randomized to early direct oral anticoagulation (n = 1,006) vs. delayed direct oral anticoagulation (n = 1,007).

In the early group, anticoagulation was given within 48 hours after a minor or moderate stroke or day 6 or 7 after a major stroke. In the delayed group, anticoagulation was given on day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12 to 14 after a major stroke.

  • Total number of enrollees: 2,013
  • Duration of follow-up: 90 days
  • Mean patient age: 77 years
  • Percentage female: 46%
  • Percentage with diabetes: 18%

Inclusion criteria:

  • Acute ischemic stroke
  • AF

Exclusion criteria:

  • Receiving anticoagulation at baseline
  • Confluent parenchymal hematoma within infarcted brain tissue
  • Intracranial hemorrhage remote from infarcted tissue

Principal Findings:

The primary outcome of vascular death, recurrent ischemic stroke, systemic embolism, major extracranial bleeding, or symptomatic intracranial hemorrhage at 30 days occurred in 2.9% of the early anticoagulation group vs. 4.1% in the delayed anticoagulation group (p = not significant [NS]).

Secondary outcomes:

  • Recurrent ischemic stroke at 30 days: 1.4% of the early anticoagulation group vs. 2.5% in the delayed anticoagulation group (p = NS)
  • Recurrent ischemic stroke at 90 days: 1.9% of the early anticoagulation group vs. 3.1% in the delayed anticoagulation group (p = NS)
  • Symptomatic intracranial hemorrhage at 30 days: 0.2% of the early anticoagulation group vs. 0.2% in the delayed anticoagulation group (p = NS)

Multivariable regression model comparing early vs. late initiation of direct oral anticoagulation according to the presence of hemorrhagic transformation:

  • Adjusted odds ratio (OR) for composite outcome at 30 days = 0.75 for no hemorrhagic transformation and 0.65 for hemorrhagic transformation (p for interaction = 0.80)
  • Adjusted OR for symptomatic intracranial hemorrhage at 30 days = 1.07 for no hemorrhagic transformation and 0.85 for hemorrhagic transformation (p for interaction = 1.00)
  • Adjusted OR for poor functional outcome at 90 days = 0.89 for no hemorrhagic transformation and 1.59 for hemorrhagic transformation (p for interaction = 0.034)

Interpretation:

Among patients with acute ischemic stroke and AF, early anticoagulation with a direct oral anticoagulant showed possible benefit compared with delayed anticoagulation; however, early anticoagulation was associated with possible worse functional outcomes compared with delayed anticoagulation. It is important to highlight that this trial was designed to provide qualitative data and did not formally test for superiority (or noninferiority) between treatment strategies. There were no apparent bleeding concerns from early anticoagulation.

References:

Rohner R, Kneihsl M, Goeldlin MB, et al., on behalf of the ELAN Investigators. Early Versus Late Initiation of Direct Oral Anticoagulants After Ischemic Stroke in People With Atrial Fibrillation and Hemorrhagic Transformation: Prespecified Subanalysis of the Randomized-Controlled ELAN Trial. Circulation 2024;May 16:[Epub ahead of print].

Fischer U, Koga M, Strbian D, et al., on behalf of the ELAN Investigators. Early Versus Later Anticoagulation for Stroke With Atrial Fibrillation. N Engl J Med 2023;388:2411-21.

Editorial: Uchino K. Anticoagulation Conundrum in Acute Ischemic Stroke With Atrial Fibrillation. N Engl J Med 2023;388:2479-80.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias, Vascular Medicine

Keywords: Anticoagulants, Atrial Fibrillation, Ischemic Stroke


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