Long-Term Benefits of N-Butylphthalide in Preventing Ischemic Stroke Recurrence: A 12-Month Prospective Study

Wei Liu,1,* Yingzhe Shao,1,* Jie Liu,2,* Juan Hao,1 Yuting Lu,3 Li Yang,1 Jinghua Wang,1,4,5 Xianjia Ning1,4,5 1Department of Neurology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Department of Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of China; 3School of Basic medical Sciences, Tianjin Medical University, Tianjin, 300070, People’s Republic of China; 4Laboratory of Epidemiology, Tianjin Neurological Institute, Tianjin, 300052, People’s Republic of China; 5Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, 300052, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xianjia Ning; Jinghua Wang, Department of Neurology, Tianjin Medical University General Hospital, Laboratory of Epidemiology, Tianjin Neurological Institute &Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, 154 Anshan Road, Heping District, Tianjin, 300052, People’s Republic of China, Tel +86-22-60817505 ; +86-22-60817504, Fax +86-22-60817448, Email [email protected]; [email protected]: This study evaluated the effects of 12 months of NBP treatment on stroke recurrence and examined the influence of age and gender on its efficacy.Methods: A prospective cohort of 1109 patients with non-cardioembolic ischemic stroke (IS) within six months was divided into NBP (n = 538) and control (n = 571) groups. The NBP group received NBP plus standard treatment, while the control group received standard treatment alone. Primary outcomes were recurrent ischemic and hemorrhagic stroke over 12 months. Secondary outcomes included functional status (modified Rankin Scale, m-RS) and all-cause mortality.Results: NBP reduced recurrent IS by 39% compared to controls (RR:0.61,95% CI:0.40– 0.93, P=0.022) and total stroke events by 39.6% (RR:0.60,95% CI:0.40– 0.91,P=0.016). Protective effects were more significant in males (RR:0.52,95% CI:0.30– 0.91, P=0.021 vs RR:0.53,95% CI:0.40– 0.91,P=0.021) and in patients under 70 years (P< 0.05). Functional outcomes (modified Rankin Scale and Barthel index) and all-cause mortality did not differ significantly between groups (all P> 0.05).Conclusion: NBP significantly reduces stroke recurrence and overall vascular events, especially in males and younger patients. While it does not improve functional outcomes or mortality, NBP demonstrates substantial preventive value for recurrent strokes.Keywords: N-butylphthalide, ischemic stroke, stroke recurrence, cardiovascular events, secondary prevention