In this multicenter retrospective study, we evaluated consecutive patients with LVO treated with IVT at three comprehensive stroke centers in China—Linyi People’s Hospital, Liaocheng People’s Hospital, and Aerospace Center Hospital—between January 2022 and December 2023. All three centers have an annual thrombolysis volume exceeding 200 cases and maintain a uniform prospective registry for the study of IVT in acute ischemic stroke. Patients were eligible for endovascular therapy when a proximal intracranial arterial occlusion was identified according to the latest international guidelines.

Patients who met the following criteria were included: (1) aged 18 and older, (2) baseline CT angiography (CTA) or MR angiography (MRA) shows occlusion in the internal carotid artery (ICA), the first (M1) or second (M2) segment of the middle cerebral artery, or the basilar artery (BA), (3) symptom onset ≤ 4.5 h, or a mismatch on CT perfusion (CTP) or MRI between diffusion-weighted imaging and fluid-attenuated inversion recovery when onset time was unknown, and (4) received IVT with 0.25 mg/kg tenecteplase or 0.9 mg/kg alteplase and a brain digital subtraction angiography (DSA).

The exclusion criteria were: extra-cranial carotid occlusion, multiple sites occlusion, missing critical imaging data or critical information, and IVT-to-puncture time more than 8 h.

Data were obtained from the registry and supplemented by reviewing medical records when necessary: age, sex, baseline and 24 h National Institutes of Health Stroke Scale (NIHSS), medical history (including hypertension, hyperlipidemia, diabetes, coronary heart disease, atrial fibrillation, previous stroke, antiplatelets use, and smoking), and time points (symptom onset, hospital arrival, IVT, groin puncture, and recanalization).

All patients received a non-contrast CT scan, either CTA or MRA at baseline, followed by subsequent DSA imaging assessments. All patient imaging was independently evaluated by two experienced radiologists at each center, who were blinded to the procedure and clinical outcomes. The following data were recorded: (1) intracranial occlusion site was identified on baseline CTA or MRA with the following categorizations: ICA, M1, M2, or BA; (2) clot burden was assessed using the clot burden score on CTA or MRA images [15]; (3) modified thrombolysis in cerebral infarction (mTICI) grade was evaluated on initial and finally DSA; (4) occlusion site on the first intracranial DSA.

Clinical outcomes were evaluated using the NIHSS at 24 h and the modified Rankin Scale (mRS) at 3 months. Early clinical improvement is defined as a reduction of the NIHSS score by ≥ 8 or achieving an NIHSS score of 0–1 at 24-h post-treatment; functional independence is defined as mRS 0–2 at 3 months. The 3-month mRS scores were determined by neurologists through telephone interviews or routine outpatient clinic visits. Care pathway information was blinded to the assessors collecting the clinical outcome data.

Early recanalization was defined as mTICI of 2b–3 (reperfusion has occurred in over 50% of the affected zone) or the absence of a retrievable thrombus on the initial DSA. We also assessed partial recanalization, defined as mTICI of 2a (reperfusion has occurred in < 50% of the affected zone). Thrombus migration was characterized as a change to a more distal occlusion on the angiogram compared to the initial occlusion on the CTA. The initial occlusion was identified as the thrombus’s most proximal location on the CTA. On the angiogram, occlusion was determined as the thrombus’s most proximal location on the initial DSA.

Safety outcomes were assessed, including: parenchymal hematomas 2 (PH- 2), defined according to the ECASS II criteria [16]; symptomatic intracranial hemorrhage (sICH) defined according to the SITS-MOST criteria [17]; and mortality, defined as an mRS score of 6.

Quantitative variables were represented by the median and interquartile range, while qualitative variables were expressed as frequency and percentage. The χ2 test, Fisher’s exact test, and Mann–Whitney U test were applied as appropriate for assessing baseline and outcome variables. The primary imaging outcome, early recanalization rates of tenecteplase and alteplase, was assessed while adjusting for baseline NIHSS score, age, occlusion site, and time from hospital arrival to puncture. Then, we evaluated primary imaging outcomes within subgroups categorized by sex (male, female), age (< 80, ≥ 80 years), NIHSS (< 15, ≥ 15), IVT-to-puncture time (< 60 and ≥ 60 min), occlusion site (ICA, M1, M2, and BA), and clot burden score (0–4, 5–7, and ≥ 8), while adjusting for pertinent covariates using logistic regression models and calculating P values for interaction (Pinteraction). Furthermore, restricted cubic splines were utilized to examine the possible nonlinear relationship between IVT-to-puncture time and early recanalization. We compared the 3-month mRS scores in two treatment groups for clinical outcomes by adjusting for baseline NIHSS score, age, and time from symptom onset to IVT. All P values reported are two-sided, with significance defined as P < 0.05. Statistical analysis was conducted with IBM SPSS version 27 and R statistics software version 4.2.2.