Evaluation of Early Versus Delayed DOACs Initiation in Acute Ischemic Stroke Patients with AF

The optimal timing for initiating direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) following acute ischemic stroke (AIS) remains a critical clinical question. This review evaluates findings from three pivotal randomized controlled trials—TIMING, ELAN, and OPTIMAS—comparing early versus delayed DOAC initiation in AF patients with AIS. Collectively, these trials provide strong evidence supporting the safety and efficacy of early initiation of DOACs in patients with AIS and AF. The TIMING trial demonstrated the non-inferiority of early DOAC initiation (≤4 days) compared to delayed initiation (5-10 days), with numerically lower rates of ischemic stroke and no cases of symptomatic ICH. The ELAN trial further corroborated these findings, showing no significant difference in the composite outcome of recurrent ischemic stroke, systemic embolism, or major hemorrhage between early initiation (≤48 h for minor/moderate strokes; days 6-7 for major strokes) and later initiation (days 3-4 to 12-14). OPTIMAS, the largest trial to date, confirmed the non-inferiority of early initiation (≤4 days) versus delayed initiation (7-14 days), without an increased risk of symptomatic ICH and with comparable rates of recurrent ischemic events.