Practical 1-2-3-4-Day Rule for Initiating Direct Oral Anticoagulants in Patients with Acute Ischemic Stroke after Endovascular Therapy: An Observational Study

Shunsuke Kimura; Noriyuki Sahara; Kuniyuki Nakamura; Tadataka Mizoguchi; Naoki Tagawa; Kota Mori; Yusuke Imamura; Takahiro Kuwashiro; Hiroshi Sugimori; Takuya Kiyohara; Yoshinobu Wakisaka; Masahiro Kamouchi; Tetsuro Ago; Ryu Matsuo

doi:10.1159/000549656

Practical 1-2-3-4-Day Rule for Initiating Direct Oral Anticoagulants in Patients with Acute Ischemic Stroke after Endovascular Therapy: An Observational Study

Cerebrovasc Dis. 2026 Jan 21:1-11. doi: 10.1159/000549656. Online ahead of print.

Authors

Shunsuke Kimura^{1

2}, Noriyuki Sahara¹, Kuniyuki Nakamura¹, Tadataka Mizoguchi¹, Naoki Tagawa¹, Kota Mori¹, Yusuke Imamura^{1

2}, Takahiro Kuwashiro^{1

2}, Hiroshi Sugimori^{1

2}, Takuya Kiyohara¹, Yoshinobu Wakisaka^{1

3}, Masahiro Kamouchi^{3

4}, Tetsuro Ago^{1

3}, Ryu Matsuo^{5

6

7}

Affiliations

¹ Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
² Division of Cerebrovascular Medicine and Neurology, National Hospitalization Organization, Kyushu Medical Center, Fukuoka, Japan.
³ Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
⁴ Department of Health Care Administration and Management, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
⁵ Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, matsuo.ryu.838@m.kyushu-u.ac.jp.
⁶ Center for Cohort Studies, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, matsuo.ryu.838@m.kyushu-u.ac.jp.
⁷ Department of Health Care Administration and Management, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, matsuo.ryu.838@m.kyushu-u.ac.jp.

PMID: 41563934
DOI: 10.1159/000549656

Abstract

Introduction: The optimal timing for initiating direct oral anticoagulants (DOACs) after endovascular therapy (EVT) for acute ischemic stroke (AIS) remains uncertain due to concerns regarding hemorrhagic complications. This study aimed to evaluate the safety and efficacy of early DOAC initiation guided by the "1-2-3-4-day" rule based on stroke severity in patients with non-valvular atrial fibrillation (NVAF) who underwent EVT.

Methods: We analyzed data from the Fukuoka Stroke Registry, a multicenter cohort including patients with AIS with NVAF who underwent EVT between 2013 and 2023. Patients were classified into the early (DOAC initiated within 1-4 days) and non-early groups. The primary outcomes were in-hospital recurrent ischemic stroke and symptomatic intracranial hemorrhage (sICH) occurring more than 24 h after EVT. The secondary outcome was a good functional outcome at 3 months (modified Rankin Scale score of 0-2). Multivariable Poisson regression and inverse probability weighting (IPW) were used for adjustment.

Results: Among the 397 patients analyzed for safety outcomes and 262 for functional outcomes, early DOAC initiation was not associated with increased risk of recurrent ischemic stroke or sICH. The proportion of patients with good functional outcome was significantly higher in the early group than in the non-early group (63.8% vs. 42.2%; adjusted risk ratio, 1.33; 95% CI, 1.06-1.66; p = 0.02). Findings remained consistent across subgroups and sensitivity analyses using IPW.

Conclusions: Early DOAC initiation following EVT based on the "1-2-3-4-day" rule was not associated with increased hemorrhagic risk; rather, it was associated with improved functional outcomes, supporting its feasibility.

Keywords: 1-2-3-4-day rule; Acute ischemic stroke; Adverse event; Direct oral anticoagulants; Endovascular therapy.