Study on the efficacy and safety of intravenous thrombolysis for acute ischemic stroke within extended time windows_West China Medical Journal

Authors：

DENG Huimin ^1,2 , WU Yi ² , LIU Jianyu ² , LI Linyan ^1,2 , XU Zhiyao ² , ZHANG Xianwen ² , ZHOU Qiang ² , XIAO Bing ² ,  LIU Hua ^1,2

1. Department of Clinical Medicine, North Sichuan Medical College, Nanchong, Sichuan 637300, P. R. China;
2. Department of Neurology, the Third People’s Hospital of Chengdu, Chengdu, Sichuan 610074, P. R. China;

Corresponding?author：

LIU Hua, Email: hxliumedidoctor@163.com

Keywords：

Acute ischemic stroke; intravenous thrombolysis; extended time windows; real-world study; functional outcome

DOI：

10.7507/1002-0179.202604057

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objectives To investigate the efficacy and safety of intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS) presenting within 4.5 to 9 hours in a Chinese real-world study, providing evidence for optimizing thrombolytic decision-making in this extended time window. Methods Patients with AIS who underwent IVT at the Third People’s Hospital of Chengdu between June 2023 and July 2025 were retrospectively enrolled. They were categorized into a standard time window group and an extended time window group based on the onset-to-treatment time. The inverse probability of treatment weighting (IPTW) method based on propensity scores was employed to balance baseline characteristics between the two groups. Multivariate logistic regression analysis was used to evaluate functional independence, the incidence of symptomatic intracerebral hemorrhage, and mortality at 3 and 6 months post-discharge. Results A total of 362 patients were enrolled, including 50 in the extended time window group and 312 cases in the standard time window group. After IPTW adjustment, baseline characteristics were well-balanced between the groups (P>0.05). Multivariate logistic regression analysis revealed that IVT in the extended time window was not an independent risk factor for modified Rankin Scale 0-1, the incidence of symptomatic intracerebral hemorrhage, or mortality (P>0.05). Conclusion In real-world clinical practice, for AIS patients strictly selected via multimodal imaging, IVT administered in the extended time window is not inferior to treatment within the standard time window regarding key outcomes such as functional independence and safety.

Citation： DENG Huimin, WU Yi, LIU Jianyu, LI Linyan, XU Zhiyao, ZHANG Xianwen, ZHOU Qiang, XIAO Bing, LIU Hua. Study on the efficacy and safety of intravenous thrombolysis for acute ischemic stroke within extended time windows. West China Medical Journal, 2026, 41(5): 729-735. doi: 10.7507/1002-0179.202604057 Copy

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2.	Wu S, Wu B, Liu M, et al. Stroke in China: advances and challenges in epidemiology, prevention, and management. Lancet Neurol, 2019, 18(4): 394-405.
3.	Wang W, Jiang B, Sun H, et al. Prevalence, incidence, and mortality of stroke in China: results from a nationwide population-based survey of 480 687 adults. Circulation, 2017, 135(8): 759-771.
4.	中華醫學會神經病學分會, 中華醫學會神經病學分會腦血管病學組. 中國急性缺血性卒中診治指南 2023. 中華神經科雜志, 2024, 57(6): 523-559.
5.	Yuan J, Lu ZK, Xiong X, et al. Age and geographic disparities in acute ischaemic stroke prehospital delays in China: a cross-sectional study using national stroke registry data. Lancet Reg Health West Pac, 2023, 33: 100693.
6.	Ye Q, Zhai F, Chao B, et al. Rates of intravenous thrombolysis and endovascular therapy for acute ischaemic stroke in China between 2019 and 2020. Lancet Reg Health West Pac, 2022, 21: 100406.
7.	Ma H, Campbell BCV, Parsons MW, et al. Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke. New England J Med, 2019, 380(19): 1795-1803.
8.	Campbell BCV, Ma H, Ringleb PA, et al. Extending thrombolysis to 4.5–9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data. Lancet, 2019, 394(10193): 139-147.
9.	Berge E, Whiteley W, Audebert H, et al. European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke. Eur Stroke J, 2021, 6(1): I-LXII.
10.	Mannism?ki L, Martinez-Majander N, Suomalainen O, et al. Comparison of functional and safety outcomes between the extended versus early time window after intravenous thrombolysis and endovascular thrombectomy. J Neurosurg Sci, 2024, 462: 123107.
11.	Xia AD, Schaefer CP, Szende A, et al. RWE framework: an interactive visual tool to support a real-world evidence study design. Drugs Real World Outcomes, 2019, 6(4): 193-203.
12.	Austin PC, Stuart EA. Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat Med, 2015, 34(28): 3661-3679.
13.	Liu L, Wang W. Risk factors for acute ischemic stroke following intravenous thrombolysis: a 2-center retrospective cohort study. Ann Palliat Med, 2022, 11(1): 185-200.
14.	Krongsut S, Piriyakhuntorn P. Unlocking the potential of HB/RDW ratio as a simple marker for predicting mortality in acute ischemic stroke patients after thrombolysis. J Stroke Cerebrovasc Dis, 2024, 33(9): 107874.
15.	Wang M, Zhang F, Guo Q, et al. Efficacy, safety, and effect on platelet activation of the timing of administration of tirofiban in patients with acute ischemic stroke. Am J Transl Res, 2025, 17(2): 791-805.
16.	Huang L, Zhang H, Li W, et al. Cerebral collateral cascade associated with infarct growth rate in ischemic stroke patients undergoing endovascular treatment. Eur J Radiol, 2025, 193: 112418.
17.	Pensato U, Demchuk AM, Menon BK, et al. Cerebral infarct growth: pathophysiology, pragmatic assessment, and clinical implications. Stroke, 2025, 56(1): 219-229.
18.	Wang Z, Jiang S, Gong C, et al. The effect of cerebral collateral recycle on outcomes for patients with large ischemic infarct undergoing endovascular treatment. J Neurol Sci, 2025, 474: 123538.
19.	Mondal R, Deb S, Ray N, et al. Advances in collateral neuroimaging for acute ischemic stroke: redefining time and tissue windows in the reperfusion era. J Neuroimaging, 2025, 35(4): e70079.
20.	Günkan A, Ferreira MY, Vilardo M, et al. Thrombolysis for ischemic stroke beyond the 4.5-hour window: a meta-analysis of randomized clinical trials. Stroke, 2025, 56(3): 580-590.
21.	Palaiodimou L, Papageorgiou NM, Safouris A, et al. Efficacy and safety of intravenous thrombolysis in the extended time window for acute ischemic stroke: a systematic review and meta-analysis.J Clin Med, 2025, 14(15): 5474.
22.	Al-Janabi OM, Jazayeri SB, Toruno MA, et al. Safety and efficacy of intravenous thrombolytic therapy in the extended window up to 24 hours: a systematic review and meta-analysis. Ann Clin Transl Neurol, 2024, 11(12): 3310-3319.
23.	Ma G, Mo R, Zuo Y, et al. Tenecteplase for acute non–large vessel occlusion 4.5 to 24 hours after ischemic stroke: the OPTION randomized clinical trial. JAMA, 2026, 335(13): 1137-1147.
24.	Turc G, Tsivgoulis G, Audebert HJ, et al. European stroke organisation – European society for minimally invasive neurological therapy expedited recommendation on indication for intravenous thrombolysis before mechanical thrombectomy in patients with acute ischaemic stroke and anterior circulation large vessel occlusion. Eur Stroke J, 2022, 7(1): I-XXVI.
25.	Qiu Z, Li F, Sang H, et al. Intravenous tenecteplase before thrombectomy in stroke. New England J Med, 2025, 393(2):139-150.

1. Feigin VL, Brainin M, Norrving B, et al. World stroke organization: global stroke fact sheet 2025. Int J Stroke, 2025, 20(2): 132-144.
2. Wu S, Wu B, Liu M, et al. Stroke in China: advances and challenges in epidemiology, prevention, and management. Lancet Neurol, 2019, 18(4): 394-405.
3. Wang W, Jiang B, Sun H, et al. Prevalence, incidence, and mortality of stroke in China: results from a nationwide population-based survey of 480 687 adults. Circulation, 2017, 135(8): 759-771.
4. 中華醫學會神經病學分會, 中華醫學會神經病學分會腦血管病學組. 中國急性缺血性卒中診治指南 2023. 中華神經科雜志, 2024, 57(6): 523-559.
5. Yuan J, Lu ZK, Xiong X, et al. Age and geographic disparities in acute ischaemic stroke prehospital delays in China: a cross-sectional study using national stroke registry data. Lancet Reg Health West Pac, 2023, 33: 100693.
6. Ye Q, Zhai F, Chao B, et al. Rates of intravenous thrombolysis and endovascular therapy for acute ischaemic stroke in China between 2019 and 2020. Lancet Reg Health West Pac, 2022, 21: 100406.
7. Ma H, Campbell BCV, Parsons MW, et al. Thrombolysis guided by perfusion imaging up to 9 hours after onset of stroke. New England J Med, 2019, 380(19): 1795-1803.
8. Campbell BCV, Ma H, Ringleb PA, et al. Extending thrombolysis to 4.5–9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data. Lancet, 2019, 394(10193): 139-147.
9. Berge E, Whiteley W, Audebert H, et al. European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke. Eur Stroke J, 2021, 6(1): I-LXII.
10. Mannism?ki L, Martinez-Majander N, Suomalainen O, et al. Comparison of functional and safety outcomes between the extended versus early time window after intravenous thrombolysis and endovascular thrombectomy. J Neurosurg Sci, 2024, 462: 123107.
11. Xia AD, Schaefer CP, Szende A, et al. RWE framework: an interactive visual tool to support a real-world evidence study design. Drugs Real World Outcomes, 2019, 6(4): 193-203.
12. Austin PC, Stuart EA. Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat Med, 2015, 34(28): 3661-3679.
13. Liu L, Wang W. Risk factors for acute ischemic stroke following intravenous thrombolysis: a 2-center retrospective cohort study. Ann Palliat Med, 2022, 11(1): 185-200.
14. Krongsut S, Piriyakhuntorn P. Unlocking the potential of HB/RDW ratio as a simple marker for predicting mortality in acute ischemic stroke patients after thrombolysis. J Stroke Cerebrovasc Dis, 2024, 33(9): 107874.
15. Wang M, Zhang F, Guo Q, et al. Efficacy, safety, and effect on platelet activation of the timing of administration of tirofiban in patients with acute ischemic stroke. Am J Transl Res, 2025, 17(2): 791-805.
16. Huang L, Zhang H, Li W, et al. Cerebral collateral cascade associated with infarct growth rate in ischemic stroke patients undergoing endovascular treatment. Eur J Radiol, 2025, 193: 112418.
17. Pensato U, Demchuk AM, Menon BK, et al. Cerebral infarct growth: pathophysiology, pragmatic assessment, and clinical implications. Stroke, 2025, 56(1): 219-229.
18. Wang Z, Jiang S, Gong C, et al. The effect of cerebral collateral recycle on outcomes for patients with large ischemic infarct undergoing endovascular treatment. J Neurol Sci, 2025, 474: 123538.
19. Mondal R, Deb S, Ray N, et al. Advances in collateral neuroimaging for acute ischemic stroke: redefining time and tissue windows in the reperfusion era. J Neuroimaging, 2025, 35(4): e70079.
20. Günkan A, Ferreira MY, Vilardo M, et al. Thrombolysis for ischemic stroke beyond the 4.5-hour window: a meta-analysis of randomized clinical trials. Stroke, 2025, 56(3): 580-590.
21. Palaiodimou L, Papageorgiou NM, Safouris A, et al. Efficacy and safety of intravenous thrombolysis in the extended time window for acute ischemic stroke: a systematic review and meta-analysis.J Clin Med, 2025, 14(15): 5474.
22. Al-Janabi OM, Jazayeri SB, Toruno MA, et al. Safety and efficacy of intravenous thrombolytic therapy in the extended window up to 24 hours: a systematic review and meta-analysis. Ann Clin Transl Neurol, 2024, 11(12): 3310-3319.
23. Ma G, Mo R, Zuo Y, et al. Tenecteplase for acute non–large vessel occlusion 4.5 to 24 hours after ischemic stroke: the OPTION randomized clinical trial. JAMA, 2026, 335(13): 1137-1147.
24. Turc G, Tsivgoulis G, Audebert HJ, et al. European stroke organisation – European society for minimally invasive neurological therapy expedited recommendation on indication for intravenous thrombolysis before mechanical thrombectomy in patients with acute ischaemic stroke and anterior circulation large vessel occlusion. Eur Stroke J, 2022, 7(1): I-XXVI.
25. Qiu Z, Li F, Sang H, et al. Intravenous tenecteplase before thrombectomy in stroke. New England J Med, 2025, 393(2):139-150.

West China Medical Journal

Study on the efficacy and safety of intravenous thrombolysis for acute ischemic stroke within extended time windows

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