Evidence map›Paper›PMID 42536265›Full record

ArticleTranslational stroke research2026

Effects of Antioxidant DI-3-N-Butylphthalide on Hemorrhagic Transformation Assessed by Propensity Score Matching in a Real-World Thrombolyzed Ischemic Stroke Patient Setting.

Ziqi Han, He Liang, Tieping Fan, Mario Minor Murakami Junior, Shumin Li, Ruikang Sun, Daoyong Peng, Shiwei Du, Yu Hasegawa, Haojie Gao and 3 more

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Article in Translational stroke research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

13 authors.

Ziqi HanDepartment of Neurology, Central Hospital of Dalian University of Technology, 826 Xi'nan Road, Dalian, 116033, Liaoning Province, China.
He LiangDepartment of Neurology, Central Hospital of Dalian University of Technology, 826 Xi'nan Road, Dalian, 116033, Liaoning Province, China.
Tieping FanDepartment of Neurointervention, Central Hospital of Dalian University of Technology, Dalian, China.
Mario Minor Murakami JuniorDivision of Neurotherapeutics, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Shumin LiDepartment of Neurology, Central Hospital of Dalian University of Technology, 826 Xi'nan Road, Dalian, 116033, Liaoning Province, China.
Ruikang SunDalian Medical University, Dalian, China.
Daoyong PengDepartment of Neurology, Central Hospital of Dalian University of Technology, 826 Xi'nan Road, Dalian, 116033, Liaoning Province, China.
Shiwei DuDepartment of Neurosurgery, South China Hospital of Shenzhen University, Shenzhen, China.
Yu HasegawaAriake Seijin Hospital, Miyano, Nagasu-machi, Tamana-gun, Kumamoto- prefecture, Japan.
Haojie GaoDepartment of Neurology, Central Hospital of Dalian University of Technology, 826 Xi'nan Road, Dalian, 116033, Liaoning Province, China.
Dong ChenInstitute of Cadio-Cerebrovascular Medicine, Dalian University of Technology, Dalian, China. neuro-chen@dlut.edu.cn.
Dirk M HermannDepartment of Neurology, University Hospital Essen, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany. dirk.hermann@uk-essen.de.
Yi LiuDepartment of Neurology, Central Hospital of Dalian University of Technology, 826 Xi'nan Road, Dalian, 116033, Liaoning Province, China. letaliu@bjmu.edu.cn.ORCID http://orcid.org/0000-0002-6835-3713

Funding

Dalian Medical Key Specialties "Summit Project" 2024ZZ041Revitalisation Talents Program of LiaoNing Province XLY1807083the Key Research and Development Program of Liaoning Province 2025ZXYYCR003the Science and Technology Innovation for Public Welfare Project of Dalian 2024JJ13PT051
6 · The paper itself

Abstract

backgroundHemorrhagic transformation (HT) remains a major complication limiting the clinical utility of intravenous thrombolysis with alteplase in acute ischemic stroke (AIS) patients. Dl-3-N-butylphthalide (dl-NBP), a neuroprotective agent, which has beneficial effects on post-ischemic microcirculation, oxidative stress, and blood-brain barrier integrity, may potentially mitigate this risk.

methodsUsing propensity score matching (1:1), this study analyzed 1,541 AIS patients of the prospective Dalian Single-center Study on Intravenous Thrombolysis for Ischaemic Stroke (DATIS) cohort treated at Central Hospital of Dalian University of Technology. Patients were stratified into combination therapy (alteplase + dl-NBP, n = 674) and monotherapy (alteplase alone, n = 674) groups. Dl-NBP (25 mg in 100 ml, 0.9% saline) was administered within 12 h after admission and followed by twice-daily doses of the same fomulation during hospitalization in the combination therapy group. Primary outcomes included the incidence of HT assessed post-thrombolysis and symptomatic intracranial hemorrhage (sICH) defined as radiographic hemorrhage occurring within 7 days post-thrombolysis and accompanied by clinical deterioration or an increase in NIHSS score ≥ 4 points. Neurological deficits at admission and at discharge were assessed using the National Institutes of Health Stroke Scale (NIHSS).

resultsAfter propensity score matching (674 patients combination therapy vs. 674 patients monotherapy), baseline characteristics were balanced (p > 0.05 for all influence variables). The alteplase + dl-NBP combination therapy group demonstrated significantly lower HT rates (2.2% vs. 6.7%, p < 0.001) and sICH incidence (0.9% vs. 3.4%, p < 0.001) than the alteplase monotherapy group. Multivariate analysis identified dl-NBP adjuvant as protective against HT (OR = 0.32, 95%CI: 0.18-0.58), while fasting glucose (OR = 1.10) and high-density lipoprotein levels (OR = 2.25) were independent risk factors. The percentage of patients exhibiting NIHSS improvements during hospitalization was significantly increased in combination therapy group compared with monotherapy group (60.8 vs. 55.3%, p = 0.041). Hospitalization costs were slightly higher in the combination therapy group (¥20,781 vs. ¥19,771, p < 0.001).

conclusionsEarly adjunctive dl-NBP administration in addition to alteplase-induced thrombolysis significantly reduces hemorrhagic complications. To our knowledge, this is the first large-scale real-world study to demonstrate that dl-NBP reduces the risk of post-thrombolytic brain hemorrhage, supporting its antioxidant benefits in a clinical setting.

Indexed as

AntioxidantsBenzofuransFibrinolytic AgentsIntracranial HemorrhagesIschemic StrokeNeuroprotective AgentsThrombolytic TherapyAgedAged, 80 and overDrug Therapy, CombinationFemaleHumansMaleMiddle AgedPropensity ScoreProspective Studies3-n-butylphthalideAntioxidantsBenzofuransFibrinolytic AgentsNeuroprotective AgentsTissue Plasminogen ActivatorAcute ischemic strokeAlteplaseBrain hemorrhageFree radical scavengerNeuroprotectionOxidative stressThrombolysis

Identifiers

PMID42536265

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.