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

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