Transl Stroke Res. 2026 Jul 31;17(4):91. doi: 10.1007/s12975-026-01470-5.
ABSTRACT
BACKGROUND: Hemorrhagic 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.
METHODS: Using 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).
RESULTS: After 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).
CONCLUSIONS: Early 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.
PMID:42536265 | DOI:10.1007/s12975-026-01470-5