Kazunori Toyoda

A timely new practice, known as the “1-2-3-4 day rule”, for the administration of direct oral anticoagulants (DOACs) in patients after acute ischemic stroke or transient ischemic attack (TIA) is deemed feasible to reduce the risk of recurrent stroke, systemic embolism and major bleeding, according to Kazunori Toyoda (Suita National Brain and Cardiovascular Center, Osaka, Japan) and research team. This is the main finding of a hospital-based combined cohort study published earlier this month in the newspaper Stroke.

Based on Combined Evidence of Acute Stroke Management with Urgent Risk Factor Assessment and Improvement in Nonvalvular Atrial Fibrillation (SAMURAI) register (September 2011-March 2014) and the RELAXED register (February 2014-April 2016) in Japan, the researchers propose an alternative time to start DOACs compared to current practice.

Toyota et al patients (n=1797) were divided into subgroups based on their history of TIA and ischemic stroke with three different severities assessed with the National Institutes of Health Stroke Scale score (mild [0–7]moderate [8–15]and severe [≥16]). Patients starting DOACs earlier than the median day of initiation in each subgroup were defined as the early treatment group. The authors note that study outcomes include recurrent stroke or systemic embolism, ischemic stroke, and major bleeding within 90 days. toyoda samurai study - 1-2-3-4 day TIA rule

Toyota et al report that DOACs were given from a median of two, three, four, and five days after TIA and mild, moderate, and severe stroke, respectively. The authors state that strokes or systemic embolisms presented less frequently in the early treatment group, starting with DOACs at one, two, three, and four days respectively, 1.9% (n=785) per compared to late treatment group (n=1012) at 3.9%. Ischemic stroke was also less common in the early group compared to the late treatment group, at 1.7% versus 3.2% respectively.

According to the researchers, in the early and late treatment groups, major bleeding events were similar at 0.8% versus 1.0% respectively. Additionally, intracranial hemorrhage and ischemic stroke were similar in the early and late treatment groups, at 0.2% versus 0.6% and 2.4% versus 2.2%, respectively. Six prospective European registries were used for external validation.

Toyota et al point out that early administration of DOACs over one, two, three or four days, depending on stroke severity, is considered feasible to reduce the risk of recurrent stroke or systemic embolism, without increasing events major hemorrhages. According to the authors, the results of this study support ongoing randomized trials to establish the most appropriate timing for DOA administration.

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