Haoxuan Zhu

Background: Whether time dependency could apply to middle cerebral artery (MCA) M2 occlusion stroke remains unclear. Objectives: To compare the association of time to EVT and clinical outcomes between large vessel occlusion (LVO) and MCA M2 occlusion patients. Design: A pool analysis of DEVT (Effect of Endovascular Treatment Alone vs Intravenous Alteplase Plus Endovascular Treatment on Functional Independence in Patients with Acute Ischemic Stroke), RESCUE BT (Effect of Intravenous Tirofiban vs Placebo Before Endovascular Thrombectomy on Functional Outcomes in Large Vessel Occlusion Stroke) and MARVEL (Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke) trial. Methods: 2,846 EVT-treated patients with onset-to-puncture (OTP) ≤24 hours were included. Associations of OTP and onset-to-reperfusion time (OTR) with clinical outcomes were evaluated in patients with LVO and MCA-M2 occlusion separately. The primary effectiveness outcome was 90-day modified Rankin Scale (mRS) score 0–2. Secondary effectiveness outcomes included ordinal mRS score and mRS score 0–1 at 90 days. Safety outcomes were 90-day mortality and symptomatic intracranial hemorrhage within 48 hours. Results: Among 2,846 eligible patients, 364 had MCA-M2 occlusion. In the LVO group, longer OTP and OTR were consistently associated with worse functional outcomes. In the MCA-M2 group, OTP was not associated with mRS score 0–2 (adjusted odds ratio [aOR] 0.98, 95% confidence interval [CI] 0.94–1.03, P =0.495) or ordinal mRS shift ( P =0.124), although it was associated with lower odds of mRS 0–1 ( P =0.036). Similarly, OTR was not associated with functional independence in MCA-M2 occlusion, but longer OTR was associated with worse ordinal mRS outcomes and lower odds of mRS 0–1. Conclusions: Treatment delay was consistently associated with worse outcomes after EVT in LVO. In MCA-M2 occlusion, the associations between time metrics and clinical outcomes demonstrated less consistent across different outcome definitions.

Background: This study aimed to investigate whether renal insufficiency (RI) modifies the effectiveness and safety of endovascular treatment (EVT) in patients with acute ischemic stroke and large infarct in a real‐world setting. Methods: This study was a post hoc analysis of a prospective multicenter cohort study. RI was defined as an estimated glomerular filtration rate 2 on admission. Patients were treated with EVT plus standard medical treatment or standard medical treatment alone and were stratified by RI status. The primary effectiveness outcome was favorable outcome (modified Rankin scale 0–3) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage and 90‐day mortality. Results: Among 745 patients with acute ischemic stroke and large infarct, 343 (46.0%) had RI and 490 (65.8%) underwent EVT. Compared with standard medical treatment, EVT was associated with improved functional outcomes (modified Rankin scale 0–3) in both the RI (adjusted odds ratio [OR] 2.55 [95% CI, 1.15–5.68], P =0.022) and the non‐RI group (adjusted OR 2.65 [95% CI, 1.49–4.73], P =0.001). EVT was also associated with higher risks of symptomatic intracranial hemorrhage in both groups ( P =0.002 and 0.007, respectively), whereas no significant difference in mortality was observed. Results were consistent in the inverse probability‐weighted analyses. No statistically significant interaction was observed between RI status and treatment effect for effectiveness or safety outcomes. Conclusions: In patients with acute ischemic stroke and large infarct, EVT was associated with improved functional outcomes but a higher risk of hemorrhagic complications. We did not find statistically significant evidence of interaction between EVT and RI status for 90‐day outcomes.

Background: Whether adjunctive intra‐arterial thrombolysis improves outcomes in patients with acute ischemic stroke due to cardioembolism remains unclear. This study aimed to investigate the efficacy and safety of adjunctive intra‐arterial urokinase in patients with acute ischemic stroke due to cardioembolism who achieved near‐complete to complete reperfusion. Methods: This study was a secondary analysis of the POST‐UK (Adjunctive Intra‐Arterial Urokinase After Near‐Complete to Complete Reperfusion for Acute Ischemic Stroke) trial, which was conducted from November 15, 2022, to March 29, 2024. Patients were randomly assigned to the intra‐arterial urokinase group or the control group. The primary outcome was disability‐free survival at 90 days, defined as a modified Rankin Scale score of 0 to 1. Safety outcomes included 90‐day all‐cause death, symptomatic intracranial hemorrhage and any intracranial hemorrhage within 48 hours. Results: Among 209 patients with cardioembolism (median age 73 [interquartile range, 63–81] years; 45.9% men), 106 were assigned to the control group and 103 to the intra‐arterial urokinase group. Compared with the control group, adjunctive intra‐arterial urokinase significantly increased the odds of disability‐free survival at 90 days (adjusted risk ratio, 1.49 [95% CI, 1.08–2.06]; P =0.01; inverse probability of treatment weighting adjusted risk ratio, 1.47 [95% CI, 1.04–2.09]; P =0.03). No significant differences were found between groups in 90‐day mortality rate, symptomatic intracranial hemorrhage, or any intracranial hemorrhage within 48 hours. Conclusions: In patients with acute ischemic stroke due to cardioembolism who achieved near‐complete to complete reperfusion, adjunctive intra‐arterial urokinase significantly improved disability‐free survival at 90 days without increasing the risk of death or intracranial hemorrhage. Registration: URL: ChiCTR.org.cn; Unique identifier: ChiCTR2200065617.

Background: Whether adjunct intra‐arterial urokinase has differential effectiveness and safety by sex among patients with acute ischemic stroke who achieve near‐complete to complete reperfusion after endovascular thrombectomy (EVT) remains unknown. Methods: This post hoc analysis of the POST‐UK (Adjunctive Intra‐Arterial Urokinase After Successful Endovascular Thrombectomy in Patients With Large‐Vessel Occlusion Stroke) multicenter randomized clinical trial included 534 patients with proximal intracranial large‐vessel occlusion who achieved near‐complete to complete reperfusion after endovascular thrombectomy. Participants were assigned to intra‐arterial urokinase or no adjunct intra‐arterial thrombolysis. The primary effectiveness outcome was 90‐day survival without disability, defined as a modified Rankin Scale score of 0 to 1. Primary safety outcomes were 90‐day all‐cause death and symptomatic intracranial hemorrhage within 48 hours. Results: Among 534 participants, 223 were female and 311 were male. The treatment‐by‐sex interaction for the primary outcome was not statistically significant ( P for interaction=0.06). In sex‐stratified analyses, intra‐arterial urokinase showed a potential benefit signal for 90‐day survival without disability among female participants (46.7% versus 32.2%; adjusted risk ratio [RR], 1.47 [95% CI, 1.07–2.02]; P =0.02), whereas no statistically significant difference was observed among male participants (44.1% versus 46.6%; adjusted RR, 0.97 [95% CI, 0.77–1.22]; P =0.79). No statistically significant differences in safety outcomes were observed between treatment groups in either sex, including 90‐day mortality and symptomatic intracranial hemorrhage. Conclusions: Adjunct intra‐arterial urokinase after endovascular thrombectomy showed a potential benefit signal for 90‐day disability‐free survival among female participants, without statistically significant differences in male participants or hemorrhagic outcomes across sex subgroups. These findings should be considered hypothesis generating and warrant confirmation in future prospective studies. Registration: URL: www.chictr.org.cn ; Unique Identifier: ChiCTR2200065617.

Objectives: Whether endovascular treatment (EVT) remained effective and safe in patients aged ≥ 80 years with large ischemic stroke was unclear. We aimed to investigate the effectiveness and safety of EVT in this population. Materials and Methods: Using data from a cohort study and randomized controlled trial, we included patients aged ≥ 80 years with large ischemic stroke treated with EVT or standard medical treatment (SMT) alone, and compared clinical outcomes between the two groups. Furthermore, EVT patients were dichotomized by age (80– 84 and ≥ 85 years) to evaluate associations between age and outcomes. The primary effectiveness outcome was the distribution of 90-day modified Rankin scale (mRS) score. Safety outcomes were 90-day mortality and symptomatic intracerebral hemorrhage within 48 hours. Results: 270 eligible patients were included, with 212 in EVT group. EVT was associated with a favorable shift in the distribution of 90-day mRS scores compared with SMT (adjusted common odds ratio 2.83, 95% confidence interval 1.48– 5.70, P=0.003). Secondary effectiveness outcomes including 90-day mRS score 0– 2, 0– 3 and 0– 4 also favored EVT. The 90-day mortality was significantly lower in EVT group (P=0.009). However, the rate of any intracerebral hemorrhage was significantly higher in EVT group (P=0.001). Notably, increasing age did not modify the treatment effect of EVT. Conclusions: Among patients aged ≥ 80 years with large ischemic stroke, EVT was associated with more favorable 90-day functional outcomes and lower mortality than SMT, but with a higher risk of intracerebral hemorrhage. The treatment effect of EVT remained consistent regardless of age in this population.

Background: The effectiveness and safety of endovascular treatment ( EVT ) compared with standard medical treatment ( SMT ) for acute basilar artery occlusion in patients with National Institutes of Health Stroke Scale ( NIHSS ) scores ≤10 remain unclear. This study aimed to investigate the effectiveness and safety of EVT versus SMT in patients with acute basilar artery occlusion with NIHSS scores ≤10. Methods: Patients with acute basilar artery occlusion and NIHSS scores ≤10 included in this study were derived from a nationwide prospective registry in China. Patients were divided into the EVT and SMT groups. The primary outcome was the distribution of modified Rankin Scale score at 90 days. Safety outcomes included death at 90 days and symptomatic intracerebral hemorrhage within 48 hours. Results: Among 106 patients, 78 (73.6%) received EVT. The median age was 64 (interquartile range, 59–71) years, and 23 (21.7%) were women. Compared with SMT, EVT was associated with a favorable shift in the distribution of modified Rankin Scale score at 90 days (adjusted odds ratio, 6.22 [95% CI, 2.31–16.73]) and lower 90‐day death (adjusted odds ratio, 0.23 [95% CI, 0.06–0.88]). There was no significant difference in the incidence of symptomatic intracerebral hemorrhage within 48 hours between the 2 groups. At 1‐year follow‐up, functional outcomes continued to favor EVT over SMT. In both groups, as the baseline NIHSS score increased, the probability of achieving favorable outcomes progressively decreased, while the probability of death increased. Conclusions: In patients with acute basilar artery occlusion and NIHSS scores of ≤10, EVT was associated with better functional outcomes and lower mortality rate.