Efficacy and safety of intravenous anticoagulation for noncardioembolic stroke: An analysis of data from the Japan Stroke Data Bank

Abstract

Background:

The benefits of parenteral anticoagulation in noncardioembolic stroke are still unclear.

Aims:

The aim of this study was to clarify the association between intravenous anticoagulation (IVAC) and clinical outcome in patients with acute noncardioembolic stroke.

Methods:

The study had an observational design and analyzed data from the Japan Stroke Data Bank, a hospital-based multicenter stroke registration database. A total of 33,184 patients were identified to have presented with acute noncardioembolic stroke between 2017 and 2020. After exclusion of patients with incomplete IVAC data, those with a premorbid modified Rankin Scale (mRS) score of 3–5, those who received thrombolysis or endovascular therapy, and those with atrial fibrillation, we examined the association between IVAC and clinical outcomes, including mRS score at discharge and the frequency of severe bleeding episodes during hospitalization.

Results:

In total, 8967 patients were enrolled. The mean age was 71.8 ± 12.3 years, 64.9% were male, and the median initial National Institutes of Health Stroke Scale score was 2. Of these 8967 patients, 5708 (63.7%) received IVAC, 6425 (71.6%) had mRS score of 0–2 at discharge, and 33 (0.4%) experienced severe bleeding. In multivariable logistic regression analysis, IVAC was associated with lower odds of mRS 0–2 at discharge (odds ratio [OR] 0.83, 95% confidence interval [CI] 0.73–0.94) but not with severe bleeding (OR 0.94, 95% CI 0.45–1.99). In subgroup analysis, a significant interaction (p < 0.001) indicated effect modification by dual antiplatelet therapy (DAPT) status, with a stronger association between IVAC and reduced odds of mRS 0–2 in patients not receiving DAPT.

Conclusions:

In this Japanese cohort, although assessed at discharge, IVAC was associated with lower odds of favorable early outcome after noncardioembolic stroke, likely influenced by selection bias, and the safety findings were inconclusive due to the small number of events

Keywords

Noncardioembolic stroke intravenous anticoagulation bleeding dual antiplatelet therapy

Get full access to this article

View all access options for this article.

References

Prabhakaran

Gonzalez

Zachrison

, et al. 2026 Guideline for the early management of patients with acute ischemic stroke: a guideline from the American Heart Association/American Stroke Association. Stroke. Epub ahead of print 26 January 2026. DOI: 10.1161/STR.0000000000000513.

International Stroke Trial Collaborative Group. The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. Lancet 1997; 349: 1569–1581.

TOAST Investigators. Low molecular weight heparinoid, ORG 10172 (Danaparoid), and outcome after acute ischaemic stroke. JAMA 1998; 279: 1265–1272.

Berge

Abdelnoor

Nakstad

, et al. Low molecular-weight heparin versus aspirin in patients with acute ischaemic stroke and atrial fibrillation: a double-blind randomised study. HAEST Study Group. Heparin in acute embolic stroke trial. Lancet 2000; 355: 1205–1210.

Bath

Lindenstrom

Boysen

, et al. Tinzaparin in acute ischaemic stroke (TAIST): a randomised aspirin-controlled trial. Lancet 2001; 358: 702–710.

Wong

Chen

, et al. Low-molecular-weight heparin compared with aspirin for the treatment of acute ischaemic stroke in Asian patients with large artery occlusive disease: a randomised study. Lancet Neurol 2007; 6: 407–413.

Wang

Ouyang

Yang

, et al. Anticoagulants for acute ischaemic stroke. Cochrane Database Syst Rev 2021; 10: CD000024.

Paciaroni

Agnelli

Micheli

Caso

Efficacy and safety of anticoagulant treatment in acute cardioembolic stroke: a meta-analysis of randomized controlled trials. Stroke 2007; 38: 423–430.

Kobayashi

Tazaki

Effect of the thrombin inhibitor argatroban in acute cerebral thrombosis. Semin Thromb Hemost 1997; 23: 531–534.

10.

Miyamoto

Ogasawara

Kuroda

, et al. Japan stroke society guideline 2021 for the treatment of stroke. Int J Stroke 2022; 17: 1039–1049.

11.

Hosomi

Naya

Kohno

Kobayashi

Koziol

; Japan Standard Stroke Registry Study Group. Efficacy of anti-coagulant treatment with argatroban on cardioembolic stroke. J Neurol 2007; 254: 605–612.

12.

Wang

Sun

, et al. Early argatroban and antiplatelet combination therapy in acute non-lacunar single subcortical infarct associated with mild intracranial atherosclerosis. BMC Neurol 2021; 21: 440.

13.

Barreto

Ford

Shen

, et al. Randomized, Multicenter Trial of ARTSS-2 (Argatroban With Recombinant Tissue Plasminogen Activator for Acute Stroke). Stroke 2017; 48: 1608–1616.

14.

Chen

Cui

Zhou

, et al. Effect of argatroban plus intravenous alteplase vs intravenous alteplase alone on neurologic function in patients with acute ischemic stroke: the ARAIS randomized clinical trial. JAMA 2023; 329: 640–650.

15.

Zhang

Zhong

Xue

, et al. Argatroban in patients with acute ischemic stroke with early neurological deterioration: a randomized clinical trial. JAMA Neurol 2024; 81: 118–125.

16.

Liu

Wang

, et al. Effect of argatroban plus dual antiplatelet in branch atherosclerosis disease: a randomized clinical trial. Stroke 2025; 56: 1662–1670.

17.

Cheng

Liu

Meng

Efficacy and safety of Argatroban in patients with acute ischemic stroke: a systematic review and meta-analysis. Front Neurol 2024; 15: 1364895.

18.

Xie

Chen

, et al. Can the combination of antiplatelet or alteplase thrombolytic therapy with argatroban benefit patients suffering from acute stroke? a systematic review, meta-analysis, and meta-regression. Plos One 2024; 19: e0298226.

19.

Wada

Yasunaga

Horiguchi

, et al. Outcomes of argatroban treatment in patients with atherothrombotic stroke: observational nationwide study in Japan. Stroke 2016; 47: 471–476.

20.

Hao

Tampi

O'Donnell

, et al. Clopidogrel plus aspirin versus aspirin alone for acute minor ischaemic stroke or high risk transient ischaemic attack: systematic review and meta-analysis. BMJ 2018; 363: k5108.

21.

Itabashi

Mori

Furui

Sato

Yazawa

Fujiwara

Combination oral antiplatelet therapy may increase the risk of hemorrhagic complications in patients with acute ischemic stroke caused by large artery disease. Thromb Res 2011; 128: 541–546.

22.

Toyoda

Yoshimura

Nakai

, et al. Twenty-year change in severity and outcome of ischemic and hemorrhagic strokes. JAMA Neurol 2022; 79: 61–69.

23.

Adams

Jr Bendixen

Kappelle

, et al et al. Classification of subtype of acute ischemic stroke. Definitions for Use in a Multicenter Clinical Trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993; 24: 35–41.

24.

Franco

Becattini

Beyer-Westendorf

, et al. Definition of major bleeding: prognostic classification. J Thromb Haemost 2020; 18: 2852–2860.

25.

Kanda

Investigation of the freely-available easy-to-use software “EZR” (Easy R) for medical statistics. Bone Marrow Transplant 2013; 48: 452–458.

26.

Committee for Stroke Guideline 2021; The Japan Stroke Society. Japan Stroke Society Guideline 2021 for the Treatment of Stroke revised version 2025. Tokyo, Japan: Kyowa-Kikaku, 2025, pp. 75–77(in Japanese).