ELAN Trial: Early Initiation of DOACs Reduces Event Risk after Stroke Event

Results of the ELAN trial offer evidence in support of an early anticoagulation strategy in patients with atrial fibrillation and stroke.

A trial with more than 2000 participants, results of the study, which compared early anticoagulation strategies against later anticoagulation strategies, suggest the early initiation strategy for direct oral anticoagulants (DOACs) following stroke in people with atrial fibrillation was associated with decreased incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days relative to later DOAC initiation.¹

The most common type of treated heart arrhythmia, atrial fibrillation’s prevalence and associated risk pose a significant threat to public, and individual-level, health. Mentioned within 183,321 death certificates in 2019, the burden of the disease is expected to grow, with estimates projecting a prevalence of 12.1 million people in the US by 2030.²

An investigator-initiated, open-label trial, the Early versus Late Initiation of Direct Oral Anticoagulants in Post-ischemic Stroke Patients with Atrial Fibrillation (ELAN) randomized trial was launched with the intent of comparing the effects of early and later initiation of DOACs in persons with atrial fibrillation who have had an acute ischemic stroke. Conducted at 103 sites in 15 countries within Europe, the Middle East, and Asia, the trial enrolled 2013 patients and randomized them in a 1:1 ratio to early anticoagulation or later anticoagulation, with assessors unaware of the trial-group assignments.¹

For the purpose of analysis, timing of initiation was based on type of stroke. Per trial protocol, early initiation began with 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke. In contrast, later initiation began on day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, and day 12, 13, or 14 following a major stroke.¹

Of the 2013 participants included in the trial, 37% were diagnosed with a minor stroke, 40% were diagnosed with a moderate stroke, and 23% were diagnosed with a major stroke. Overall, 1006 were assigned to early anticoagulation and 1007 were assigned to later anticoagulation. The entire study cohort had a median age of 77 (IQR, 70 to 84) years, 45% were female, and the median National Institutes of Health Stroke Scale Investigators was 5 (IQR, 2 to 11) at admission and 3 (IQR, 1 to 6) at randomization. Investigators noted baseline demographic and clinical characteristics were similar in both treatment groups.¹

The primary outcome of interest for the trial was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization. Secondary outcomes of interest for the trial included the individual components of the composite endpoint at 30 and 90 days.¹

Upon analysis, primary outcome events were recorded among 2.9% of the early-treatment group compared to 4.1% among the later-treatment group (risk difference, —1.18 percentage points [95% confidence interval [CI], —2.84 to 0.47]) at 30 days. When assessing the primary outcome at 90 days, results indicated a primary outcome event occurred in 3.7% of the early-treatment group compared to 5.6% of the later-treatment group (risk difference, —1.92 percentage points [95% CI, —3.82 to —0.02]).¹

Further analysis of secondary endpoints revealed recurrent ischemic stroke occurred among 1.4% in the early-treatment group compared to 2.5% of the later-treatment group at 30 days (Odds ratio [OR], 0.57 [95% CI, 0.29 to 1.07]). Analysis of recurrent ischemic stroke at 90 days revealed a similar trend, with such an event occurring in 1.9% of the early-treatment group and 3.1% of the later-treatment group at 90 days (OR, 0.60 [95% CI, 0.33 to 1.06]). Investigators highlighted symptomatic intracranial hemorrhage occurred in 2 participants in both groups at 30 days.¹

“This trial was designed to estimate the treatment effects of early initiation and later initiation of DOACs and the degree of precision of this estimate. No statistical hypothesis was tested for superiority or noninferiority, and the results are intended to provide qualitative data that may be of use to clinicians,” wrote investigators.¹

References:

1. Fischer U, Strbian D, Koga M. Early versus Later Anticoagulation for Stroke with Atrial Fibrillation. The New England Journal of Medicine. Published online May 24, 2023. doi:10.1056/NEJMoa2303048
2. Atrial fibrillation. Centers for Disease Control and Prevention. October 14, 2022. Accessed May 24, 2023. https://www.cdc.gov/heartdisease/atrial_fibrillation.htm.