Abstract Background and aims We aimed to assess the effect of time to treatment on clinical outcomes in patients who received intravenous tenecteplase versus standard medical treatment between 4.5 and 24 hours after last known well (LKW). Methods This secondary analysis of the Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-III (TRACE-III) trial explored the association of LKW-to treatment time, analyzed as both categorical (4.5-9, 9-16, and 16-24 hours) and continuous variables, with 90-day functional outcomes and safety outcomes including symptomatic intracranial hemorrhage and mortality. Results Among 516 patients, 134 were treated within 4.5-9 hours, 232 within 9-16 hours, and 150 within 16-24 hours after LKW. The primary outcome (mRS 0-1) occurred in 31.9% versus 23.1% of patients receiving tenecteplase and standard medical treatment within 4.5-9 hours (adjusted odds ratio [aOR], 1.37; 95% confidence interval [CI], 0.59 to 3.17; adjusted P=0.470); 30.6% versus 21.3% within 9-16 hours (aOR, 1.69; 95%CI, 0.88 to 3.25; adjusted P=0.115); and 38.0% versus 29.1% within 16-24 hours (aOR, 1.98; 95%CI, 0.92 to 4.29; adjusted P=0.081). There was no statistically significant association between each 1-hour treatment delay and efficacy outcomes or symptomatic intracranial hemorrhage in either treatment arm, whereas mortality exhibited an inverse trend, with lower rates observed with longer treatment delays. Overall, no significant interaction between LKW-to-treatment time and treatment assignments was discovered (all p for interaction >0.1). Conclusions Collectively, these findings support the use of tenecteplase in TRACE-III-qualified patients throughout the entire 4.5-24-hour window and highlight the potential for extending the therapeutic window beyond 24 hours. Conflict of interest

Importance:Whether intravenous tenecteplase prior to endovascular treatment (EVT) for ischemic stroke reduces disability in the late time window is unclear. Objective:To investigate the adverse events and efficacy of tenecteplase prior to EVT in patients 4.5 to 24 hours after ischemic stroke onset due to proximal middle cerebral artery (MCA) occlusion. Design, Setting, and Participants:Multicenter, phase 3, randomized, open-label, blinded end point, superiority trial conducted at 40 centers in China. Adult (≥18 years) patients with acute ischemic stroke 4.5 to 24 hours after last known to be well due to MCA-M1 or proximal M2 occlusion with salvageable brain tissue (ischemic core volume <70 mL, mismatch ratio ≥1.8, and mismatch volume ≥15 mL) identified on computed tomography-perfusion or magnetic resonance-perfusion-diffusion imaging were enrolled from January 25, 2024, through July 21, 2025, and followed up for 90 days. Final follow-up occurred on October 14, 2025. Interventions:Eligible patients were randomly assigned in a 1:1 ratio to receive intravenous tenecteplase (0.25 mg/kg; maximum dose, 25 mg) before EVT (n = 199) or EVT alone (n = 192). Main Outcomes and Measures:The primary outcome was functional independence, defined as a score of 0 to 2 on the modified Rankin Scale (range, 0-6, with higher scores indicating greater disability) at 90 days. Adverse events outcomes included symptomatic intracranial hemorrhage and death. Results:All of the 391 patients enrolled (median age, 68 years [IQR, 59-75]; 155 [39.6%] females) completed the trial. Functional independence at 90 days occurred in 88 patients (44.2%) in the tenecteplase before EVT group and 83 patients (43.2%) in the EVT alone group (adjusted relative rate, 1.01 [95% CI, 0.83-1.24]; P = .89; risk difference, 0.99% [95% CI, -8.84% to 10.83%]). Mortality within 90 days was 12.7% (25/197) in the tenecteplase before EVT group and 14.2% (27/190) in the EVT alone group. Symptomatic intracranial hemorrhage within 36 hours was 5.1% (10/197) and 2.6% (5/190), respectively. Conclusions and Relevance:In patients presenting to EVT-capable centers 4.5 to 24 hours after stroke onset with proximal MCA occlusion, intravenous tenecteplase before EVT did not improve clinical outcomes vs EVT alone. Trial Registration:ClinicalTrials.gov Identifier: NCT06221371.

The TRACE-3 trial established the efficacy of intravenous tenecteplase for patients with acute ischemic stroke and large vessel occlusion in the late time window. It remains unclear whether intravenous tenecteplase confers clinical benefits specifically in the subpopulation of patients who did not achieve successful large vessel recanalization. This is a post-hoc analysis of the TRACE-3 trial, a multicenter randomized controlled trial comparing tenecteplase with standard medical therapy in patients with large vessel occlusion between 4.5 and 24 h of symptom onset. The analysis included participants who had failed recanalization (defined as an Arterial Occlusive Lesion [AOL] score of 0) on follow-up angiography at 24 h. Primary outcome of current study was functional independence (modified Rankin Scale [mRS] score 0–2) at 90 days. We assessed effect modification by baseline characteristics, including stroke severity (National Institutes of Health Stroke Scale [NIHSS]) and collateral circulation status. Among 288 patients with failed recanalization (123 in the tenecteplase group and 165 in the control group), tenecteplase was associated with a significantly higher rate of functional independence at 90 days compared with standard medical therapy (42.3

INTRODUCTION:The hypoperfusion intensity ratio (HIR) was significantly correlated with the futile reperfusion (FR) and National Institutes of Health Stroke Scale (NIHSS) score. We aimed to quantify the direct and indirect effect of HIR on FR. METHODS:We analyzed acute ischemic stroke patients with large vessel occlusion who underwent endovascular treatment at seven comprehensive stroke centers between 2017 and 2022 in China. HIR was automatically calculated on baseline perfusion imaging as the ratio of brain volume with time-to-max (Tmax) delay >10 s over volume with Tmax >6 s. The established threshold HIR >0.4 was regarded as poor tissue-level collaterals (TLCs). FR was defined as the modified Rankin Scale score of 4-6 at 90 days despite successful recanalization. Mediation analysis using the "mediation" package in R 4.2.2 was performed to examine the potential causal chain. RESULTS:Among the 891 included patients, FR was observed in 320 (35.9%) patients. Inadequate TLC was significantly associated with a higher NIHSS score (adjusted common odds ratio [OR], 1.47; 95% confidence interval [CI], 1.12-1.93; p = 0.006) and higher rates of FR (aOR, 1.87; 95% CI, 1.31-2.68; p = 0.001) within 90 days. The baseline NIHSS score was a predictor of FR (aOR, 1.13; 95% CI, 1.10-1.16; p < 0.001). Causal mediation analyses revealed that 20.4% (95% CI, 5.5%-40.9%) of the relationship between HIR and FR was mediated by the baseline NIHSS score. CONCLUSION:Higher NIHSS score partially mediates the association between poorer HIR and FR at 90 days among patients after EVT. Our study provided primarily mechanistic and prognostic findings about the effect of HIR on FR.

BACKGROUND:We aimed to explore whether the benefits of tenecteplase within 4.5 to 24 h would be modified by the infarct growth rate (IGR). METHODS:This study is a secondary analysis of the Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-III (TRACE-III) trial, a Phase 3, multicenter, prospective, open-label, randomized, blinded-outcome-assessment trial. In the TRACE-III trial, patients with large-vessel occlusion at 4.5 to 24 h without thrombectomy were enrolled at 58 centers in China and randomly assigned to receive 0.25 mg/kg tenecteplase or standard medical treatment. Of these, patients with witnessed stroke onset time were analyzed. The IGR was calculated as baseline ischemic core volume divided by time since onset. The primary outcome was the modified Rankin Scale (mRS) 0-1 at 90 days. The treatment effect of tenecteplase versus standard medical treatment was assessed in two groups based on the median IGR cut point. A multiplicative interaction term for IGR*treatment was used to test for effect modification. RESULTS:In 292 eligible patients, the median IGR was 1.4 ml/h. A total of 146 patients with IGR < 1.4 ml/h were classified as ultraslow IGR (Tenecteplase, 70; Standard medical treatment, 76), and 146 patients with IGR ⩾ 1.4 ml/h were classified as slow IGR (Tenecteplase, 73; Standard medical treatment, 73). The rate of no disability (mRS ⩽ 1) was significantly increased with tenecteplase in slow progressors (34.2% vs 15.1%; OR = 2.94, 95% CI 1.32 to 6.55; P = 0.009). The functional status was similar in ultraslow progressors (mRS 0-1: 37.1% vs 35.5%; OR = 1.07, 95% CI 0.55 to 2.11; P = 0.84). A P value for the interaction between IGR and treatment was 0.06. The incidence of sICH and mortality did not differ significantly between the two treatment regimens in the IGR groups. CONCLUSION:Patients with late-window ischemic stroke who are not eligible for endovascular thrombectomy may derive greater benefit from tenecteplase compared with standard medical treatment among those with relatively faster infarct growth, although this finding should be considered exploratory.

BACKGROUND:The efficacy and safety of intravenous thrombolysis with tenecteplase within 24 h after stroke onset due to basilar artery occlusion are not well studied. We aimed to assess whether intravenous tenecteplase administered within 24 h after symptom onset improved functional outcome compared with standard medical treatment in patients with basilar artery occlusion. METHODS:TRACE-5 was a prospective, randomised, open-label, blinded-endpoint, superiority, phase 3 trial conducted at 66 stroke centres in China. We included patients aged 18 years or older with stroke due to basilar artery occlusion who were eligible for intravenous thrombolytics within 24 h of stroke onset or the time they were last known to be well and had a pre-stroke modified Rankin scale (mRS) score of 3 or less (scores range from 0 to 6, with higher scores indicating greater disability). Patients were randomly assigned to receive a single intravenous bolus of tenecteplase (0·25 mg/kg; maximum 25 mg) within 24 h after symptom onset or standard medical treatment (which could include intravenous alteplase at 0·9 mg/kg, maximum 90 mg, within 4·5 h of symptom onset; anticoagulation; or antiplatelets), with or without endovascular thrombectomy. The primary outcome was a score of 0-1 on the mRS or return to the baseline mRS score (if the baseline pre-stroke mRS score was 2-3) at 90 days. Safety outcomes were symptomatic intracranial haemorrhage and death. The primary outcome and safety outcomes were assessed in all randomly assigned participants included in their originally assigned groups. This trial is registered with ClinicalTrials.gov, NCT06196320. FINDINGS:Between Jan 24, 2024, and June 20, 2025, 452 patients were enrolled (mean age 66·4 years [SD 11·2], 321 [71%] males, and 131 [29%] females), of whom 222 (49%) subsequently underwent thrombectomy; 221 were randomly assigned to receive tenecteplase and 231 to receive standard medical treatment. Alteplase was used in 80 (35%) of the patients in the standard medical treatment group. An mRS score of 0-1 or return to the baseline mRS score occurred in 83 (38%) patients in the tenecteplase group and 66 (29%) patients in the standard medical treatment group (adjusted relative rate 1·50 [95% CI 1·09-2·08], p=0·014). Symptomatic intracranial haemorrhage within 36 h occurred in four (2%) patients in the tenecteplase group and seven (3%) patients in the standard medical treatment group (adjusted relative rate 0·58 [95% CI 0·17-1·99]). All-cause mortality at 90 days was similar between groups (65 [29%] patients in the tenecteplase group and 71 [31%] patients in the standard medical treatment group; adjusted relative rate 0·87 [95% CI 0·62-1·22]), as was the proportion of patients with an mRS score of 5-6 at 90 days (82 [37%] vs 89 [39%]; 0·87 [0·65-1·18]). INTERPRETATION:In this trial involving Chinese patients with ischaemic stroke due to basilar artery occlusion, tenecteplase within 24 h after stroke onset improved functional outcome compared with standard medical treatment. The incidence of symptomatic intracranial haemorrhage and death was similar. FUNDING:Noncommunicable Chronic Diseases-National Science and Technology Major Project, Beijing Municipal Science Fund for Distinguished Young Scholars, National Natural Science Foundation of China, and China Shijiazhuang Pharmaceutical Company Recomgen Pharmaceutical (Guangzhou).

Abstract Background and aims Whether sex influence thrombolysis outcomes beyond 4.5 hours remains unclear. We aimed to investigate potential sex-based disparities in outcomes of late-window tenecteplase thrombolysis. Methods The Tenecteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events–III (TRACE-III) trial is a phase 3, multicenter, prospective, open-label, randomized, blinded-outcome-assessment trial, including patients with large-vessel occlusion at 4.5 to 24 hours without thrombectomy who were enrolled at 58 centers in China and randomly assigned to receive 0.25mg/kg tenecteplase or standard medical treatment. In this secondary analysis, we compared outcomes after tenecteplase versus control, stratified by sex. We also compared outcomes in female versus male patients treated with tenecteplase. The primary outcome was modified Rankin scale (mRS) 0-1 at 90 days. Sex-related effect modification was examined. Results Women accounted for 166 (32.2%) of 516 patients enrolled in the TRACE-III trial. Eighty-one (48.8%) of 166 women and 183 (52.3%) of 350 men received tenecteplase thrombolysis. Among male participants, the tenecteplase group achieved significantly higher rates of mRS 0-1 at 90 days compared with control (36.6% tenecteplase, 25.7% control, OR 1.67 [95% CI, 1.05–2.64]). Among female participants, the primary outcome was similar between groups (24.7% tenecteplase, 21.2% control, OR 1.22 [95% CI, 0.59–2.52]). No significant sex-based differences were observed for the primary outcome (P for interaction= 0.48) and other efficacy or safety outcomes. Conclusions Tenecteplase treatment benefit was maintained in both women and men without increasing safety concerns. Thrombolysis should be equally considered for patients of both sex meeting eligibility criteria in late-time windows. Conflict of interest All authors have nothing to disclose.

RATIONALE AND OBJECTIVES:Half of ischemic stroke patients are subject to futile reperfusion (FR) after endovascular treatment (EVT). The hypoperfusion intensity ratio (HIR) represents tissue-level collaterals (TLC). We aimed to evaluate the predictive performance of HIR in the assessment of FR. MATERIALS AND METHODS:Retrospective data were derived from a multicenter cohort study of patients with large vessel occlusion in the anterior circulation who underwent EVT in China. HIR was automatically calculated on baseline perfusion imaging as the ratio of brain volume with Tmax >10 s over volume with Tmax >6 s. Poor TLC was regarded as HIR >0.4. The primary outcome was FR, defined as modified Rankin Scale score of 4-6 at 90 days despite successful recanalization. Safety outcomes were symptomatic intracranial hemorrhage (sICH) within 36 h and all-cause mortality at 90 days. RESULTS:A total of 910 patients were included, and we observed FR in 325 (35.7%) patients after EVT. More frequent FR at 90 days was seen in patients with poor TLC (50.2% vs. 30.1%; odds ratio [OR], 2.34; 95% confidential interval [CI], 1.74-3.25; P<0.001). In multivariable regression, the higher HIR was independently associated with higher odds of FR (adjusted OR, 1.88; 95% CI, 1.31-2.68; P=0.001). The rates of sICH were not significantly different between the two groups. HIR>0.4 was correlated with higher rates of 90-day mortality even after adjusting covariates. CONCLUSION:Poorer HIR on admission perfusion imaging was strongly associated with FR occurrence after EVT. This automated and rapidly available perfusion parameter might help the identification of stroke patients at risk of FR.

Abstract Background and aims Bridging therapy failed to show additional benefit to direct endovascular treatment (EVT) in proximal middle cerebral artery (MCA) in the late time window when EVT is immediately available. We aimed to explore whether the duration between randomization and artery revascularization after EVT influences the effect of bridging thrombolytic on patient outcomes in the late time window for patients with acute ischemic stroke due to proximal MCA occlusion. Methods We performed a secondary analysis using data from the endovascular treatment with or without preceding intravenous Tenecteplase in Patients with Late-window acUte ischemic Stroke due to middle cerebral artery occlusion (TNK-PLUS) trial (NCT06221371), a phase 3, multicenter, prospective, randomized, open-label, blinded-endpoint trial, which enrolled 391 patients from 40 centers in China with MCA M1 or proximal M2 occlusion, presenting within 4.5 to 24 hours after symptom onset. Participants were randomly allocated 1:1 to receive either intravenous tenecteplase prior to EVT (intervention) or direct EVT (control). The primary outcome was modified Rankin Scale score of 0-2 at 90 days. We included 374 patients from the TNK-PLUS population who achieved artery revascularization after EVT, and assessed whether efficacy of tenecteplase bridging EVT versus direct EVT could be modified by time from randomization to revascularization. Results We have finished the TNK-PLUS main results analysis, and will have the subgroup results by ESOC. Conclusions The TNK-PLUS subgroup analysis of randomization to revascularization time may improve understanding of the role of bridging therapy in the late time window and may facilitate patient selection for transfer trials. Conflict of interest

Importance Whether intravenous tenecteplase prior to endovascular treatment (EVT) for ischemic stroke reduces disability in the late time window is unclear. Objective To investigate the adverse events and efficacy of tenecteplase prior to EVT in patients 4.5 to 24 hours after ischemic stroke onset due to proximal middle cerebral artery (MCA) occlusion. Design, Setting, and Participants Multicenter, phase 3, randomized, open-label, blinded end point, superiority trial conducted at 40 centers in China. Adult (>= 18 years) patients with acute ischemic stroke 4.5 to 24 hours after last known to be well due to MCA-M1 or proximal M2 occlusion with salvageable brain tissue (ischemic core volume <70 mL, mismatch ratio >= 1.8, and mismatch volume >= 15 mL) identified on computed tomography-perfusion or magnetic resonance-perfusion-diffusion imaging were enrolled from January 25, 2024, through July 21, 2025, and followed up for 90 days. Final follow-up occurred on October 14, 2025. Interventions Eligible patients were randomly assigned in a 1:1 ratio to receive intravenous tenecteplase (0.25 mg/kg; maximum dose, 25 mg) before EVT (n = 199) or EVT alone (n = 192). Main Outcomes and Measures The primary outcome was functional independence, defined as a score of 0 to 2 on the modified Rankin Scale (range, 0-6, with higher scores indicating greater disability) at 90 days. Adverse events outcomes included symptomatic intracranial hemorrhage and death. Results All of the 391 patients enrolled (median age, 68 years [IQR, 59-75]; 155 [39.6%] females) completed the trial. Functional independence at 90 days occurred in 88 patients (44.2%) in the tenecteplase before EVT group and 83 patients (43.2%) in the EVT alone group (adjusted relative rate, 1.01 [95% CI, 0.83-1.24]; P = .89; risk difference, 0.99% [95% CI, -8.84% to 10.83%]). Mortality within 90 days was 12.7% (25/197) in the tenecteplase before EVT group and 14.2% (27/190) in the EVT alone group. Symptomatic intracranial hemorrhage within 36 hours was 5.1% (10/197) and 2.6% (5/190), respectively. Conclusions and Relevance In patients presenting to EVT-capable centers 4.5 to 24 hours after stroke onset with proximal MCA occlusion, intravenous tenecteplase before EVT did not improve clinical outcomes vs EVT alone.

Importance Trials have not demonstrated superiority of alteplase or tenecteplase vs standard care in patients with mild stroke and have raised safety concerns. Prourokinase is an alternative fibrinolytic that may have a favorable safety profile, and the benefit-risk profile of prourokinase in mild stroke is unknown. Objective To investigate the efficacy and safety of prourokinase in mild ischemic stroke within 4.5 hours of symptom onset. Design, Setting, and Participants This was a multicenter, prospective, open-label, blinded–end point randomized clinical trial conducted from November 2022 through December 2023 with 3 months of follow-up. The trial was conducted at 89 hospitals in China. Patients with a baseline National Institutes of Health Stroke Scale score of 5 or less (scores range from 0-42, with higher scores indicating more severe neurological deficit) within 4.5 hours from the time the patient was last known to be well. Patients with intention to proceed to endovascular treatment were excluded. Interventions Eligible patients were randomly assigned in a 1:1 ratio to receive prourokinase, 35 mg (15-mg bolus + 20-mg infusion over 30 minutes) or standard care, including antiplatelet or anticoagulant therapy, at the discretion of local investigators. Main Outcomes and Measures The primary outcome was modified Rankin Scale score of 0 or 1 (range, 0-6, with higher scores indicating greater disability) at day 90. Safety outcomes were symptomatic intracranial hemorrhage and death. Results Of 3836 patients who underwent screening, 1446 (37.7%) were enrolled in the trial. Median (IQR) age was 65.9 (57.7-72.7) years, and 948 were male (65.5%). A total of 723 patients were assigned to prourokinase and 723 to standard care. The primary outcome occurred in 639 patients (88.5%) in the prourokinase group and 658 (91.0%) in the standard care group (relative risk, 0.97; 95% CI, 0.94-1.01; 2-sided P = .12). Symptomatic intracranial hemorrhage was 0.7% (5 of 723 patients) with prourokinase and 0% with standard care, and mortality at 90 days was 2.3% and 1.4%, respectively. Conclusions and Relevance Results of this randomized clinical trial demonstrate that prourokinase was not superior to standard care to improve the functional outcomes for patients with mild ischemic stroke within 4.5 hours after symptom onset but had a similar safety profile. Trial Registration ClinicalTrials.gov Identifier: NCT05507645

Background The benefit–risk profile of tenecteplase in the elderly patients with acute ischaemic stroke (AIS) is uncertain. We sought to investigate the efficacy and safety of 0.25 mg/kg tenecteplase compared with alteplase for AIS patients aged ≥80 years.Methods We performed a post hoc analysis of the Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-2 Trial, a randomised, phase 3, non-inferiority clinical trial. Disabling AIS patients aged ≥80 years who initiated intravenous thrombolytics within 4.5 hours of symptom onset were enrolled from June 2021 to May 2022 across 53 centres in China and were randomly allocated to receive 0.25 mg/kg tenecteplase or 0.9 mg/kg alteplase. The primary efficacy outcome was the proportion of participants with a modified Rankin Scale (mRS) score of 0–1 at 90 days. Symptomatic intracranial haemorrhage (sICH) within 36 hours was the safety outcome.Results Of 137 participants, mRS 0–1 at 90 days occurred in 37 (49.3%) of 75 in the tenecteplase group vs 20 (33.9%) of 59 in the alteplase group (risk ratio (RR) 1.47, 95% CI 0.96 to 2.23). sICH within 36 hours was observed in 3 (4.0%) of 76 in the tenecteplase group and two (3.3%) of 61 in the alteplase group (RR 1.30, 95% CI 0.20 to 8.41).Conclusions The risk–benefit profile of tenecteplase thrombolysis was preserved in the elderly patients, which lends further support to intravenous 0.25 mg/kg tenecteplase as an alternative to alteplase in these patients.

Importance:Trials have not demonstrated superiority of alteplase or tenecteplase vs standard care in patients with mild stroke and have raised safety concerns. Prourokinase is an alternative fibrinolytic that may have a favorable safety profile, and the benefit-risk profile of prourokinase in mild stroke is unknown. Objective:To investigate the efficacy and safety of prourokinase in mild ischemic stroke within 4.5 hours of symptom onset. Design, Setting, and Participants:This was a multicenter, prospective, open-label, blinded-end point randomized clinical trial conducted from November 2022 through December 2023 with 3 months of follow-up. The trial was conducted at 89 hospitals in China. Patients with a baseline National Institutes of Health Stroke Scale score of 5 or less (scores range from 0-42, with higher scores indicating more severe neurological deficit) within 4.5 hours from the time the patient was last known to be well. Patients with intention to proceed to endovascular treatment were excluded. Interventions:Eligible patients were randomly assigned in a 1:1 ratio to receive prourokinase, 35 mg (15-mg bolus + 20-mg infusion over 30 minutes) or standard care, including antiplatelet or anticoagulant therapy, at the discretion of local investigators. Main Outcomes and Measures:The primary outcome was modified Rankin Scale score of 0 or 1 (range, 0-6, with higher scores indicating greater disability) at day 90. Safety outcomes were symptomatic intracranial hemorrhage and death. Results:Of 3836 patients who underwent screening, 1446 (37.7%) were enrolled in the trial. Median (IQR) age was 65.9 (57.7-72.7) years, and 948 were male (65.5%). A total of 723 patients were assigned to prourokinase and 723 to standard care. The primary outcome occurred in 639 patients (88.5%) in the prourokinase group and 658 (91.0%) in the standard care group (relative risk, 0.97; 95% CI, 0.94-1.01; 2-sided P = .12). Symptomatic intracranial hemorrhage was 0.7% (5 of 723 patients) with prourokinase and 0% with standard care, and mortality at 90 days was 2.3% and 1.4%, respectively. Conclusions and Relevance:Results of this randomized clinical trial demonstrate that prourokinase was not superior to standard care to improve the functional outcomes for patients with mild ischemic stroke within 4.5 hours after symptom onset but had a similar safety profile. Trial Registration:ClinicalTrials.gov Identifier: NCT05507645.

ABSTRACT Background Whether to use tenecteplase for acute ischemic stroke patients in the extended window has so far been little studied. Methods In this meta‐analysis, we included all the randomized controlled trials comparing tenecteplase with control at 4.5 to 24 h after the last known well of acute ischemic stroke with large vessel occlusion. A systematic search was performed in PubMed, Web of Science, Embase, and Cochrane Central Register of Controlled Trials databases, up to 12th June, 2024. Our primary outcome was an excellent functional outcome with a modified Rankin scale score (mRS) of 0–1 at 90 days. Our safety outcomes included mRS 5–6 at 90 days, mortality within 90 days, symptomatic intracranial hemorrhage and parenchymal hematoma Type 2. Results Ultimately, three studies involving 1198 patients were included in the pooled analysis, where tenecteplase exhibited a higher rate of mRS 0–1 at 90 days (OR, 1.36; 95%CI, 1.07–1.75; p = 0.01) and recanalization (OR, 3.30; 95%CI, 1.59–6.84; p = 0.001). For other outcomes, no significant differences were found between groups. Conclusions: This meta‐analysis of randomized controlled trials manifested that tenecteplase within a 4.5‐ to 24‐h time window of large vessel occlusion stroke was superior to control for an excellent functional outcome (mRS 0–1) without safety concerns.

Currently,reperfusion therapy targeting the ischemic penumbra is the preferred treatment for acute ischemic stroke.The continuous advancements in neuroimaging techniques for the ischemic penumbra have provided more evidence for reperfusion therapy based on tissue window.This review summarized the significant progress of the ischemic penumbra over the past 50 years,focused on the current neuroimaging assessment methods of ischemic penumbra,including the widely used ischemic hypoperfusion-infarct core or clinical symptom-infarct core mismatch and emerging techniques such as multiphase CTA,ASL,etc.Additionally,this paper compared 5 mainstream automatic post-processing software of image in the market,aiming to provide reference for clinical reperfusion diagnosis and treatment.

Although intravenous thrombolysis with alteplase remains the primary treatment for acute ischemic stroke, tenecteplase has shown potential advantages over alteplase. Animal studies have demonstrated the favorable pharmacokinetics and pharmacodynamics of tenecteplase. Moreover, it is easier to administer. Clinical trials have demonstrated that tenecteplase is not inferior to alteplase and may even be superior in cases of acute ischemic stroke with large vessel occlusion. Current evidence supports the time and cost benefits of tenecteplase, suggesting that it could potentially replace alteplase as the main option for thrombolytic therapy, especially in patients with large vessel occlusion.

IntroductionTo compare the perfusion volumes assessed by a new automated CT perfusion (CTP) software iStroke with the circular singular value decomposition software RAPID and determine its predictive value for functional outcome in patients with acute ischaemic stroke (AIS) who underwent endovascular treatment (EVT).MethodsData on patients with AIS were collected from four hospitals in China. All patients received CTP followed by EVT with complete recanalisation within 24 hours of symptom onset. We evaluated the agreement of CTP measures between the two softwares by Spearman’s rank correlation tests and kappa tests. Bland-Altman plots were used to evaluate the agreement of infarct core volume (ICV) on CTP and ground truth on diffusion-weighted imaging (DWI). Logistic regression models were used to test the association between ICV on these two softwares and functional outcomes.ResultsAmong 326 patients, 228 had DWI examinations and 40 of them had infarct volume >70 mL. In all patients, the infarct core and hypoperfusion volumes on iStroke had a strong correlation with those on RAPID (ρ=0.68 and 0.66, respectively). The agreement of large infarct core (volume >70 mL) was substantial (kappa=0.73, p<0.001) between these two softwares. The ICV measured by iStroke and RAPID was significantly correlated with independent functional outcome at 90 days (p=0.009 and p<0.001, respectively). In patients with DWI examinations and those with an ICV >70 mL, the ICV of iStroke and RAPID was comparable on individual agreement with ground truth.ConclusionThe automatic CTP software iStroke is a reliable tool for assessing infarct core and mismatch volumes, making it clinically useful for selecting patients with AIS for acute reperfusion therapy in the extended time window.

Cerebrovascular clinicians from different countries all over the world made great progress in the diagnosis and treatment of cerebral vascular diseases in recent years.Numerous high-quality clinical studies cover multiple fields and hotspots of cerebral vascular disease,such as thrombectomy/thrombolysis in the acute phase of ischemic stroke,intervention for atrial fibrillation,blood pressure management and other acute phase intervention measures,providing solid and reliable evidence-based medical evidence for clinical diagnosis and treatment in cerebral vascular disease,and promoting the reduction of cerebral vascular disease burden.This paper reviews the important clinical research progress in the field of cerebral vascular disease in 2023,helping readers better understand the advantages and great significance of these clinical studies,and looking forward to more and better cerebral vascular disease clinical studies in the future.