Related Experiment Video
Updated: Jun 4, 2025
The WATCHMAN Left Atrial Appendage Closure Device for Atrial Fibrillation
Published on: February 28, 2012
Early vs Late Anticoagulation After Ischemic Stroke in Patients With Atrial Fibrillation and Covert Brain Infarcts
Markus Kneihsl1,2,3, Arsany Hakim4, Martina B Goeldlin5
1Department of Neurology, Medical University of Graz, Austria.
Insights
Early direct oral anticoagulant (DOAC) initiation significantly reduces recurrent stroke risk in patients with atrial fibrillation and covert brain infarcts (CBIs). This early treatment strategy for ischemic stroke (IS) patients with CBIs shows no increased harm, aiding clinical decisions.
Area of Science:
- Neurology
- Cardiology
- Clinical Trials
Background:
- Covert brain infarcts (CBIs) are linked to higher stroke recurrence in patients with first-ever ischemic stroke (IS) and atrial fibrillation (AF).
- The impact of early versus late direct oral anticoagulant (DOAC) initiation on stroke recurrence in IS patients with AF and CBIs remains unclear.
Purpose of the Study:
- To determine if CBIs influence the effectiveness of early versus late DOAC treatment in patients experiencing their first IS with AF.
- To assess the safety and efficacy of early DOAC initiation in preventing recurrent ischemic events in this patient subgroup.
Main Methods:
- A post hoc analysis of the randomized ELAN trial involving 1,694 patients with first-ever IS and AF.
- Comparison of early (<48 hours to 14 days) versus late DOAC initiation based on stroke severity.
- Outcomes were analyzed based on the presence or absence of CBIs identified on prerandomization imaging.
Main Results:
- Forty percent (678/1,694) of participants had CBIs.
- Early DOAC initiation was associated with a reduced risk of IS recurrence in patients with CBIs (aRD: -2.7%, 95% CI -5.0 to -0.4).
- No significant reduction in IS recurrence was observed in patients without CBIs, and no symptomatic intracranial hemorrhage was noted in the early treatment group.
Conclusions:
- The presence of CBIs may identify a specific patient group with IS and AF who benefit most from early DOAC initiation to prevent recurrent ischemic events.
- Early DOAC treatment in patients with CBIs appears safe, with no increase in observed harm.
- Findings support considering early DOAC treatment for patients with stroke and AF, particularly those with evidence of CBIs.
Background And Objectives:
Covert brain infarcts (CBIs) in patients with first-ever ischemic stroke (IS) and atrial fibrillation (AF) are associated with an increased risk of stroke recurrence. We aimed to assess whether CBIs modify the treatment effect of early vs late initiation of direct oral anticoagulants (DOACs) in patients with IS and AF.
Methods:
We conducted a post hoc analysis of the international, multicenter, randomized-controlled ELAN trial, which compared early (<48 hours after ischemic stroke for minor and moderate stroke, 6-7 days for major stroke) vs late (>48 hours for minor, 3-4 days for moderate, 12-14 days for major stroke) initiation of DOACs in patients with IS and AF. The primary outcome was a composite of recurrent IS, symptomatic intracranial hemorrhage (sICH), major extracranial bleeding, systemic embolism, or vascular death within 30 days after stroke; secondary outcomes were the individual components. We estimated outcomes based on the presence of CBIs (any CBI vs no CBI) on prerandomization imaging (core-lab rating) using adjusted risk differences (aRDs) between treatment arms. Point estimates and 95% CIs are presented without reporting p values.
Results:
Of the 1,694 participants with first-ever IS included (median age: 77 years, 45.9% female), 678 (40.0%) had CBI. The imaging core-lab interrater reliability for the presence of CBI was 0.87 (0.81-0.94). The primary outcome occurred in 8 (2.3%; recurrent IS: 3/342) of 342 participants with CBI assigned to the early treatment arm vs 20 (6.0%; recurrent IS: 12/336) of 336 assigned to the late treatment arm (aRD: -3.6%, 95% CI -6.6 to -0.6) (p for interaction: 0.063). With early DOAC treatment, IS recurrence risk was lower in participants with CBI (aRD: -2.7%, 95% CI -5.0 to -0.4), but not in participants without CBI (aRD: -0.4, 95% CI -2.1 to 1.2). No sICH was observed in the early treatment group.
Discussion:
The presence of CBI may indicate a subgroup of patients with first-ever IS and AF who particularly benefits from early DOAC initiation to prevent ischemic event recurrence, without increasing harm. Our findings should be considered in clinical decision making regarding timely DOAC treatment in patients with stroke and AF.
Classification Of Evidence:
This study provides Class II evidence that in patients with covert brain infarcts, atrial fibrillation, and first-ever ischemic stroke, early (vs late) initiation of DOACs is associated with lower risk of recurrent stroke with no increase in harm.
Trial Registration Information:
URL: clinicaltrials.gov/study/NCT03148457; Unique identifier: NCT03148457; submitted: April 7, 2017; first patient enrolled: November 6, 2017.
