Early anticoagulation after stroke decreases recurrence without increasing bleeding in patients with atrial fibrillation

1. Recurrent ischemic stroke rates were significantly reduced in patients who started DOAC within 4 days of an acute ischemic stroke versus those who started therapy at 5 days and later.

2. The rate of symptomatic intracerebral hemorrhage was similar between groups.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Recurrent ischemic events are a major concern after acute ischemic stroke in people with atrial fibrillation. The optimal time to start direct oral anticoagulants (DOACs) remains uncertain as clinicians must balance embolic prevention against the risk of intracranial bleeding. This systematic review and meta-analysis aimed to compare starting a DOAC within 4 days of stroke onset versus waiting until day 5 or later in adults with acute ischemic stroke and atrial fibrillation. The primary outcome of the study was a 30-day composite of recurrent ischemic stroke and symptomatic intracranial hemorrhage, while key secondary outcome was recurrent ischemic stroke within 30 days. According to study results, early DOAC initiation reduced recurrent ischemic stroke without increasing symptomatic intracerebral hemorrhage. This study was strengthened by a large sample size, contributing to the generalizability of results.

Click to read the study in The Lancet

Relevant Reading: Early versus Later Anticoagulation for Stroke with Atrial Fibrillation

In-depth [systematic review and meta-analysis]: A thorough review of PubMed, Cochrane, and Embase was conducted from inception to Mar 16, 2025. Included were patients ≥ 18 years old with acute ischemic stroke and atrial fibrillation who were randomized to receive a DOAC either within 4 days of stroke onset or ≥ 5 days. Altogether, 5,429 patients (2,683 who started early and 2,746 who started later) were included in the final analysis. The primary composite of recurrent ischemic stroke, symptomatic intracerebral hemorrhage, or unclassified stroke within 30 days occurred less frequently in the early treatment group compared to the later group (2.1% vs 3.0%, odds ratio [OR] 0.70, 95% confidence interval [CI] 0.50–0.98, p<0.05). The secondary outcome of recurrent ischemic stroke within 30 days was also reduced with early DOAC initiation (1.7% vs 2.6%; OR 0.66, 95% CI 0.45–0.96, p<0.05), without an increase in symptomatic intracranial hemorrhage (0.4% in both groups, p=0.96). Findings from this study suggest that starting DOAC within 4 days of acute ischemic stroke in atrial fibrillation lowers the risk of recurrent stroke without increasing bleeding risk.

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