A new timely practice—known as the “1-2-3-4-day” rule—for the administration of direct oral anticoagulants (DOACs) in patients after acute ischaemic stroke or transient ischaemic attack (TIA) is deemed feasible to decrease the risk of recurrent stroke, systemic embolism, and major bleeding, according to Kazunori Toyoda (National Cerebral and Cardiovascular Center in Suita, Osaka, Japan) and research team. This is the main concluding finding of a combined hospital-based cohort study published earlier this month in the journal Stroke.
Based on the combined data of stroke acute management with urgent risk-factor assessment and improvement-non-valvular atrial fibrillation (SAMURAI) registry (September 2011–March 2014) and the RELAXED registry (February 2014–April 2016) in Japan, the researchers propose an alternative timing for starting DOACs compared to current practice.
Toyoda et al allocated patients (n=1,797) into subgroups according to their history of TIA and ischaemic 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 initiation day in each subgroup were defined as the early treatment group. The authors note that study outcomes include recurrent stroke or systemic embolism, ischaemic stroke, and major bleeding within 90 days. 
Toyoda et al report that DOACs were administered from a median of two, three, four, and five days after TIA and mild, moderate, and severe strokes, respectively. The authors claim that stroke or systemic embolism presented less commonly within the early treatment group, starting with DOACs within one, two, three, and four days respectively,1.9% (n=785) compared to the late treatment group (n=1,012) at 3.9%. Ischaemic stroke was also less common in the early group compared to the late treatment group, at 1.7% vs. 3.2% respectively.
According to the researchers, across both the early and late treatment groups major bleeding events were similar at 0.8% vs. 1.0% respectively. Additionally, intracranial haemorrhage and ischaemic stroke were similar in both early and late treatment groups, at 0.2% vs. 0.6% and 2.4% vs. 2.2%, respectively. Six European prospective registries were used for external validation.
Toyoda et al highlight that early administration of DOACs within one, two, three, or four days, in relation to stroke severity, is deemed feasible in decreasing the risk of recurrent stroke or systemic embolism, with no increase in major bleeding events. According to the authors, the findings of this study support ongoing randomised trials to establish the most appropriate timing of DOAC administration.
