Abstract: Objective  To analyze the early therapeutic effects of tenecteplase versus alteplase in patients with acute ischemic stroke (AIS), clarify the efficacy differences between the two intravenous thrombolytic agents, and provide evidence-based references for the individualized selection of clinical intravenous thrombolysis regimens. 
Methods  Patients with AIS who received intravenous thrombolysis in the Department of Neurology, Central Hospital Affiliated to Shenyang Medical College from January 2020 to December 2023 were retrospectively and consecutively enrolled. These patients were divided into a tenecteplase group and an alteplase group according to the medication regimen. Baseline data of the two groups were collected, including age, gender, past medical history, onset-to-needle time, and baseline NIHSS score. NIHSS scores were recorded at baseline and multiple time points after intravenous thrombolysis (24 h, 72 h, 7 d, 14 d, 90 d). A linear mixed-effects model was used for statistical analysis, with a focus on the effect of the group×time interaction term on the rate of neurological function recovery. Meanwhile, residual normality test, homogeneity of variance test, multicollinearity diagnosis, and leave-one-out robustness validation were performed to ensure the reliability of the model. 
Results  A total of 580 AIS patients were included, with 300 (51.7%) in the tenecteplase group and 280 (48.3%) in the alteplase group. Compared with the alteplase group, the tenecteplase group had significantly higher baseline NIHSS scores [(16.2±4.5) points vs. (14.1±4.2) points] and a higher proportion of patients with a history of atrial fibrillation (28.3% vs. 20.7%), with both differences statistically significant (both P<0.05). Linear mixed-effects model analysis showed that: ①The main effect of group was significant (β=1.80, 95%CI 0.27-3.33, P=0.03), and the NIHSS score in the tenecteplase group was significantly higher than that in the alteplase group at baseline; ②The main effect of time was significant (β=-0.60, 95%CI -0.72--0.48, P<0.01), indicating that the NIHSS scores of both groups showed a downward trend over time; ③The group×time interaction effect was significant (β=-0.40, 95%CI -0.63--0.17, P<0.01), suggesting that the NIHSS scores decreased more rapidly in the tenecteplase group than in the alteplase group; ④Among the covariate effects, age (β=0.08, 95%CI 0.02-0.14, P=0.02) and baseline NIHSS score (β=0.85, 95%CI 0.67-1.03, P<0.01) were independent influencing factors for neurological function recovery. Model validation results indicated a good goodness of fit. 
Conclusions  After adjusting for baseline confounding factors, tenecteplase achieves faster short-term neurological function recovery than alteplase in AIS patients, and thus can serve as one of the preferred regimens for intravenous thrombolysis in ultra-early AIS (onset≤4.5 h).

Key words: Acute ischemic stroke; Intravenous thrombolysis; Tenecteplase; Alteplase; Neurological function recovery; Linear mixed-effects model

摘要： 目的 分析替奈普酶与阿替普酶在急性缺血性卒中（acute ischemic stroke，AIS）患者中的早期治疗效果，明确两种静脉溶栓药物的疗效差异，为临床静脉溶栓方案的个体化选择提供循证参考。 
方法 回顾性连续纳入2020年1月—2023年12月在沈阳医学院附属中心医院神经内科接受静脉溶栓治疗的AIS患者，根据用药方案分为替奈普酶组和阿替普酶组。收集两组患者的基线资料，包括年龄、性别、既往病史、发病至溶栓时间及基线NIHSS评分等，并提取基线及静脉溶栓后多个时间点（24 h、72 h、7 d、14 d、90 d）的NIHSS评分。采用线性混合效应模型进行统计分析，重点关注分组×时间交互项对神经功能恢复速度的影响；同时通过残差正态性检验、方差齐性检验、多重共线性诊断及留一法稳健性验证确保模型的可靠性。
结果 共纳入580例AIS患者，替奈普酶组300例（51.7%），阿替普酶组280例（48.3%）。与阿替普酶组相比，替奈普酶组基线NIHSS评分[（16.2±4.5）分 vs.（14.1±4.2）分]、心房颤动病史比例（28.3% vs. 20.7%）更高，差异均具有统计学意义（均P<0.05）。线性混合效应模型分析显示，①分组主效应显著（β=1.80，95%CI 0.27～3.33，P=0.03），提示基线时替奈普酶组NIHSS评分显著高于阿替普酶组；②时间主效应显著（β=-0.60，95%CI -0.72～-0.48，P<0.01），提示两组患者的NIHSS评分均随时间呈下降趋势；③分组×时间交互效应显著（β=-0.40，95%CI -0.63～-0.17，P<0.01），表明替奈普酶组的NIHSS评分下降速度快于阿替普酶组；④协变量效应中，年龄（β=0.08，95%CI 0.02～0.14，P=0.02）、基线NIHSS评分（β=0.85，95%CI 0.67～1.03，P<0.01）是神经功能恢复的独立影响因素。模型验证结果显示拟合优度良好。
结论 在校正基线混杂因素后，替奈普酶治疗的AIS患者短期神经功能恢复速度快于阿替普酶，替奈普酶可作为AIS超早期（发病时间≤4.5 h）静脉溶栓的优选方案之一。

关键词: 急性缺血性卒中; 静脉溶栓; 替奈普酶; 阿替普酶; 神经功能恢复; 线性混合效应模型