Explore the vast range of titles available.

Background Ischemic stroke, accounting for 85% of stroke cases, leads to severe disabilities and increased mortality. Its global incidence rose by 87.55% from 1990 to 2019, posing significant health and economic burdens. The BRICS-plus nations—Brazil, Russia, India, China, South Africa, and five others—represent a large global population, presenting unique public health challenges. This study aims to evaluate the epidemiological trends and variations in the burden of ischemic stroke across BRICS-plus nations in a timely manner. Methods Data on the number, all-age rate, age-standardized rate, and relative change in ischemic stroke disability-adjusted life years (DALYs) from 1992 to 2021 within BRICS-plus were obtained from the Global Burden of Disease Study (GBD) 2021. Relationships between the DALYs rate and the Socio-demographic Index (SDI) were evaluated using Pearson correlation analyses. Additionally, age-period-cohort modeling was employed to estimate net drift, local drift, age, period, and cohort effects over the past three decades. Results From 1992 to 2021, total DALYs due to ischemic stroke increased by 47.14%, while the age-standardized DALYs rate decreased by 33.79%. All BRICS-plus countries exhibited a declining trend in the age-standardized DALYs rate over the past three decades. Egypt reported the highest age-standardized DALYs rate (2,462.60 per 100,000 population) in 2021, whereas the most substantial reduction of 59.37% was observed in Brazil. The annual net drift in the ischemic stroke DALYs rate ranged from -3.04% for Brazil to -0.48% for Egypt among the ten countries. A significant positive correlation was observed between the DALYs rate of ischemic stroke and SDI values. Countries exhibited similar age effect patterns, with an increasing risk of DALYs rate with advancing age. Period and cohort effects highlighted declines in observed nations, indicating improved ischemic stroke management strategies. Conclusion The burden of ischemic stroke showed an overall declining trend across the BRICS-plus from 1992 to 2021, but persistent health inequalities between these countries were driven by socioeconomic disparities. Furthermore, it emphasizes the necessity for targeted interventions across age, period, and cohort dimensions to address the distinct challenges posed by ischemic stroke in these rapidly developing countries.

BackgroundDespite successful reperfusion after thrombectomy for large vessel occlusion (LVO) stroke, up to half of patients are dependent or dead at 3-month follow-up.The aim of the current study is to demonstrate safety and efficacy of administering adjunct intra-arterial (IA) tenecteplase in anterior circulation LVO patients who have achieved successful reperfusion defined as eTICI 2b50 to 3.MethodsANGEL-TNK is a multicentre, open-label, assessor-blinded endpoint, prospective randomised, controlled trial that will enrol up to 256 patients. Patients who meet inclusion criteria with anterior circulation LVO stroke and successful reperfusion will be randomised to receive IA tenecteplase or best medical management at 1:1 ratio.ResultsThe primary endpoint is a 90-day excellent outcome defined as modified Rankin Scale (mRS) 0–1. The primary safety endpoint is symptomatic intracranial haemorrhage within 48 hours from randomisation. Secondary endpoints include 90-day ordinal mRS, mRS 0–2, mRS 0–3, all-cause mortality and any intracranial haemorrhage.ConclusionIn patients with anterior circulation LVO stroke, the ANGEL-TNK trial will inform whether adjunct IA tenecteplase administered after successful thrombectomy reperfusion improves patient outcomes.Trial registration number NCT05624190.

Background and purposeThe benefits of thrombolytic therapy before endovascular thrombectomy in cases of acute ischaemic stroke, with a large infarction volume, remain unclear. This analysis aims to evaluate the effectiveness and safety of bridging therapy and endovascular therapy among patients with large cerebral infarctions.MethodsIn this post-hoc analysis of the multicentre prospective study of ANGEL-ASPECT (Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core), participants were divided into two groups: an endovascular therapy group and a bridging therapy group. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. The primary safety outcome was symptomatic intracranial haemorrhage. Ordinal logistic regression was performed to compare the primary endpoint between the two groups. Subgroup analyses were conducted to further explore potential risk factors associated with the outcomes.Results122 patients were included, of whom 77 (63%) underwent endovascular therapy and 45 (37%) underwent bridging therapy. The median scores on mRS at 90 days of the bridging therapy group and the endovascular therapy group were 3 (2–5) and 4 (2–6), with no significant differences (common OR 1.36; 95% CI 0.71 to 2.61). Symptomatic intracranial haemorrhage was reported in three patients who were in the endovascular and bridging therapy groups (relative risk (RR) 1.71; 95% CI 0.36 to 8.12). The mortality between two groups did not differ (RR 0.75; 95% CI 0.37 to 1.54).ConclusionsOur study indicated that endovascular therapy alone might be a viable option for patients with large cerebral infarctions, displaying no noticeable disparity in outcomes compared with bridging therapy.

Table 1 Comparison of all six ‘large core’ trials Trial TENSION LASTE TESLA RESCUE-Japan LIMIT SELECT-2 ANGEL-ASPECT Official title Efficacy and Safety of Thrombectomy in Stroke With Extended Lesion and Extended Time Window Large Stroke Therapy Evaluation - ASPECTS 0–5 Thrombectomy for Emergent Salvage of Large Anterior Circulation Ischemic Stroke Randomized Controlled Trial of Endovascular Therapy for Acute Large Vessel Occlusion With Large Ischemic Core A Randomized Controlled Trial to Optimize Patient’s Selection for Endovascular Treatment in Acute Ischemic Stroke Study of EVT in Acute Anterior Circulation LVO Patients with a largE infarCT core NCT number NCT03094715 IN EXTREMIS NCT03805308 NCT03702413 NCT03876457 NCT04551664 Country Austria, Canada, Czechia, Denmark, France, Germany, Norway, Slovakia, Spain USA, Europe United States Japan United States (Canada，Europe） China Imaging inclusion criteria NCCT or DWI ASPECTS 3–5 NCCT or DWI ASPECTS 0–5 NCCT ASPECTS 2–5 CT-ASPECTS 3–5 or DWI-ASPECTS 3–5; 1. ASPECT <3 and core 70–100 cc NIHSS score 5 >6 ≥6 ≥6 6–30 Age (years) >18 18–80 18–85 >18 18–85 18–80 Time <12 hour LSW <6.5 hour LKW Random <24 hour Random <6 hour LKW, 6–24 FLAIR (-) Treat <24 hour (0–12vs6–24） Random <24 hour Primary outcome mRS score shift analysis mRS score at 90& and 180 days Utility-weighted 90-day mRS score mRS score 0–3 at 90 days Shift on 90-day mRS score mRS score at 90 days Actual study start date July 20, 2018 – July 16, 2019 November 2018 October 11, 2019 September 28, 2020 Estimated primary completion date August 31, 2020 – July 16, 2022 November 2020 May 1, 2021 November 2022 Core：rCBF <30% on CT perfusion or ADC<620; Information source：https://clinicaltrials.gov. and Website. Outcomes may vary significantly in the same ASPECTS category depending on infarct volume.4 Moreover, ischemic changes in some areas of the brain are difficult to grade for ischemia on non-contrast CT (NCCT) using the ASPECTS criteria, leading to interoperator variability in ASPECTS, as was seen in the TENSION trial.5 An inaccurate ASPECTS can mis-assign the subgroup of patients eligible for ‘class I treatment guideline of ASPECTS >5’ into the untreated group, or the subgroup patients not eligible for the ‘class I treatment guideline’ into the treatment group, weakening the conclusions from the trial. The benefit of EVT in patients with favorable ASPECTS regardless of large’ CTP-defined core in the early window has been confirmed in multiple RCTs, and EVT for these patients is recommended by guidelines endorsed by many stroke societies.13–15 Choosing to randomize these patients is difficult to defend in applications to institutional review boards regulating the clinical trials in China.

In a trial conducted in China, patients with large cerebral infarctions as determined by imaging criteria within 24 hours after onset had better outcomes with endovascular therapy than with medical therapy alone.

In 340 Chinese patients with basilar-artery occlusion, endovascular treatment resulted in better neurologic outcomes than medical care. Approximately one third of patients underwent intravenous thrombolysis.

AbstractObjectiveTo assess whether intra-arterial tenecteplase administered after successful endovascular recanalisation improves outcomes in patients with acute arterial occlusion of the posterior circulation.DesignMulticentre randomised controlled trial.Setting31 hospitals in China, 24 January 2023 to 24 August 2023.Participants208 patients with successful recanalisation (grade 2b50-3 on the extended thrombolysis in cerebral infarction scale) of an occlusion in the V4 segment of the vertebral artery; proximal, middle, or distal segment of the basilar artery; or P1 segment of the posterior cerebral artery: 104 were randomly allocated to receive tenecteplase and 104 to receive standard care.InterventionsIntra-arterial tenecteplase (0.0625 mg/kg, maximum dose 6.25 mg) administered proximal to the residual thrombus (if still present) or distal to the origin of the main pontine perforator branches over 15 seconds, or endovascular treatment only (control group).Main outcome measuresThe primary outcome was freedom from disability (modified Rankin scale score 0 or 1) at 90 days after randomisation. Primary safety outcomes included symptomatic intracranial haemorrhage within 36 hours and all cause mortality at 90 days. All efficacy and safety analyses were conducted by intention to treat and adjusted for age, pre-stroke modified Rankin scale score, time from onset of moderate to severe stroke (National Institutes of Health stroke scale score ≥6) to randomisation, hypertension, and baseline stroke severity.ResultsAt 90 days, 36 patients (34.6%) in the tenecteplase group and 27 (26.0%) in the control group had a modified Rankin scale score of 0 or 1 (adjusted risk ratio 1.36, 95% confidence interval 0.92 to 2.02; P=0.12). Mortality at 90 days was similar between the tenecteplase and control groups: 29 (27.9%) v 28 (26.9%), adjusted risk ratio 1.13, 0.73 to 1.74. Symptomatic intracranial haemorrhage within 36 hours occurred in eight patients (8.3%) in the tenecteplase group and three (3.1%) in the control group (adjusted risk ratio 3.09, 0.78 to 12.20).ConclusionsIn patients with acute ischaemic stroke due to acute posterior large or proximal vessel occlusion, intra-arterial tenecteplase administered after successful recanalisation was not associated with a statistically significant reduction in combined disability and mortality at 90 days.Trial registrationClinicalTrials.gov NCT05684172.

Unsuccessful recanalisation or reocclusion after thrombectomy is associated with poor outcomes in patients with large vessel occlusion (LVO) acute ischaemic stroke (LVO-AIS). Bailout angioplasty or stenting (BAOS) could represent a promising treatment for these patients. We conducted a randomised controlled trial with the aim to investigate the safety and efficacy of BAOS following thrombectomy in patients with LVO. ANGEL-REBOOT was an investigator-initiated, multicentre, prospective, randomised, controlled, open-label, blinded-endpoint clinical trial conducted at 36 tertiary hospitals in 19 provinces in China. Participants with LVO-AIS 24 h after symptom onset were eligible if they had unsuccessful recanalisation (expanded Thrombolysis In Cerebral Infarction score of 0–2a) or risk of reocclusion (residual stenosis >70%) after thrombectomy. Eligible patients were randomly assigned by the minimisation method in a 1:1 ratio to undergo BAOS as the intervention treatment, or to receive standard therapy (continue or terminate the thrombectomy procedure) as a control group, both open-label. In both treatment groups, tirofiban could be recommended for use during and after the procedure. The primary outcome was the change in modified Rankin Scale score at 90 days, assessed in the intention-to-treat population. Safety outcomes were compared between groups. This trial was completed and registered at ClinicalTrials.gov (NCT05122286). From Dec 19, 2021, to March 17, 2023, 706 patients were screened, and 348 were enrolled, with 176 assigned to the intervention group and 172 to the control group. No patients withdrew from the trial or were lost to follow-up for the primary outcome. The median age of patients was 63 years (IQR 55–69), 258 patients (74%) were male, and 90 patients (26%) were female; all participants were Chinese. After random allocation, tirofiban was administered either intra-arterially, intravenously, or both in 334 [96%] of 348 participants. No between-group differences were observed in the primary outcome (common odds ratio 0·86 [95% CI 0·59–1·24], p=0·41). Mortality was similar between the two groups (19 [11%] of 176 vs 17 [10%] of 172), but the intervention group showed a higher risk of symptomatic intracranial haemorrhage (eight [5%] of 175 vs one [1%] of 169), parenchymal haemorrhage type 2 (six [3%] of 175 vs none in the control group), and procedure-related arterial dissection (24 [14%] of 176 vs five [3%] of 172). Among Chinese patients with unsuccessful recanalisation or who are at risk of reocclusion after thrombectomy, BAOS did not improve clinical outcome at 90 days, and incurred more complications compared with standard therapy. The off-label use of tirofiban might have affected our results and their generalisability, but our findings do not support the addition of BAOS for such patients with LVO-AIS. Beijing Natural Science Foundation, National Natural Science Foundation of China, National Key R&D Program Beijing Municipal Administration of Hospitals Incubating Program, Shanghai HeartCare Medical Technology, HeMo (China) Bioengineering, Sino Medical Sciences Technology.

Among 550 patients with stroke due to large-vessel occlusion who had presented within 4.5 hours after onset, 90-day functional outcomes were better with intravenous tenecteplase before thrombectomy than with thrombectomy alone.