News Release

Early initiation of direct oral anticoagulants after ischemic stroke with atrial fibrillation according to the “1-2-3-4-day” rule

Peer-Reviewed Publication

National Cerebral and Cardiovascular Center

Researchers at the National Cerebral and Cardiovascular Center (NCVC) in Japan propose the new optimal timings for starting direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation (NVAF) after acute ischemic stroke, based on their results from combined registry dataset. They proposed the “1-2-3-4-day” rule that DOACs are started earlier after the index event than the current recommendations.


Suita, Japan -- Anticoagulation with DOACs for secondary stroke prevention is standard therapy, but the optimal timing for starting DOACs after stroke remains unclear. A new study led by Dr. Kazunori Toyoda at the NCVC shows that relatively early initiation of DOACs decreases the risk of stroke recurrence without safety concern. The study has been published in the scientific journal StrokeR.


Early anticoagulation can decrease a risk of recurrent stroke and embolic events but may increase a risk of secondary hemorrhagic transformation of brain infarcts. The 1-3-6-12-day rule is a known consensus with graded increase in delay of anticoagulation between 1 and 12 days after onset of ischemic stroke or transient ischemic attack (TIA), according to neurological severity based on European expert opinions. However, this rule might be somewhat later than currently used in a real-world practical setting.


The researchers combined the dataset of two multicenter registries, SAMURAI-NVAF and RELAXED, for both the NCVC played a central role, and divided 1797 stroke/TIA patients in the dataset into four groups: TIA, mild stroke, moderate stroke, and severe stroke. The median days of starting DOACs in the four groups were 2, 3, 4, and 5 days after stroke onset.


When the patients starting DOACs at a day before the median days (1, 2, 3, and 4 days) or earlier were compared with those starting at the median days or later, the former patients showed a significantly lower risk of stroke or systemic embolism and a similar risk of major bleeding. The results were externally validated using the combined dataset of 6 European registry studies, where the early patients and late patients divided by our “1-2-3-4” day cutoff showed similar efficacy and safety.


The first author, Dr. Shunsuke Kimura, concludes that the present “1-2-3-4-day rule” seems to be feasible in the real-world clinical setting by careful exclusion of patients with factors favoring delayed initiation of anticoagulation such as huge infarcts, hemorrhagic transformation of infarcts, and uncontrolled hypertension.




The research has been published in Stroke as “The practical “1-2-3-4-day” rule for starting direct oral anticoagulants after ischemic stroke with atrial fibrillation: combined hospital-based cohort study” (DOI: 10.1161/STROKEAHA.121.036695).

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.