Early Anticoagulation Within Two Weeks of Stroke Onset Shows Better Outcomes in AF Patients: Study
USA: A recent randomized clinical trial evaluating the optimal timing for initiating anticoagulation after an ischemic stroke in patients with atrial fibrillation found no single best day for starting treatment. However, the findings suggest that beginning anticoagulation earlier, within the first two weeks of stroke onset, may be more beneficial than delaying it further.
The study was published online in JAMA Neurology on March 31, 2025.
Clinical guidelines recommend starting anticoagulation within two weeks after a stroke in patients with atrial fibrillation, but the ideal timing within this period remains unclear. Striking a balance between preventing recurrent embolic events and minimizing the risk of serious bleeding is crucial. To address this, Steven J. Warach, Dell Medical School, University of Texas at Austin, and colleagues aimed to determine whether a specific delay in initiating direct oral anticoagulants (DOACs) after stroke could optimize patient outcomes by reducing the risk of both ischemic and hemorrhagic events.
For this purpose, the researchers conducted a phase 2 randomized clinical trial between June 2017 and June 2023 at acute care hospitals in Texas. The study included patients with mild to moderate ischemic stroke due to atrial fibrillation who were prescribed a direct oral anticoagulant within two weeks of stroke onset. Patients were randomized within 3 to 4 days into groups starting treatment on day 3 or 4, day 6, day 10, or day 14. The primary outcome was a composite of ischemic or hemorrhagic events within 30 days. Randomization was adjusted over time to identify the optimal initiation timing.
Key Findings:
- The trial included 200 patients, with 50% being female and a median age of 75 years.
- Among the participants, 17.5% were Asian, Black, or multiracial, and 16.5% were Hispanic.
- The median National Institutes of Health Stroke Scale (NIHSS) score was 6.5, and the median lesion diameter was 3.1 cm.
- No ischemic events occurred in group 1, while 3 were reported in group 2, and 2 each in groups 3 and 4.
- Hemorrhagic events were recorded as 1 in groups 1, 2, and 3, with none in group 4.
- The probability of being the optimal time for treatment initiation was highest for group 1 (0.41), followed by group 2 (0.26), group 3 (0.17), and group 4 (0.15).
- Response-adaptive randomization was feasible and favored earlier anticoagulation initiation.
"The study did not identify a single optimal day to start direct oral anticoagulants for secondary stroke prevention in patients with atrial fibrillation. However, the findings, along with evidence from larger trials, suggest that earlier initiation within the first two weeks after stroke onset is more beneficial than delaying treatment," the authors concluded.
Reference:
Warach SJ, Davis LA, Lawrence P, et al. Optimal Delay Time to Initiate Anticoagulation After Ischemic Stroke in Atrial Fibrillation: A Pragmatic, Response-Adaptive Randomized Clinical Trial. JAMA Neurol. Published online March 31, 2025. doi:10.1001/jamaneurol.2025.0285
