Different dosing regimens of Tenecteplase in acute ischemic stroke: A network meta-analysis of the clinical evidence.

Introduction: Acute ischemic stroke remains the major cause of death and disability and conclusive evidence of Tenecteplase in treating stroke is lacking. Objective: To conduct a meta-analysis to determine whether Tenecteplase produces better outcomes than Alteplase and a network meta-analysis comparing the different dosing regimens of Tenecteplase. Methods: Searches were made in MEDLINE, CENTRAL, and ClinicalTrials.gov. The outcome measures are recanalization, early neurological improvement, functional outcomes at 90 days (modified Rankin Scale 0-1 and 0-2), intracranial hemorrhage, symptomatic intracranial hemorrhage, and mortality within 90 days from treatment. Results: Fourteen studies are included in the meta-analyses and 18 studies in the network meta-analyses. In the meta-analysis, Tenecteplase 0.25 mg/kg has significant results in early neurological improvement (OR = 2.35, and 95% CI = 1.16-4.72) and excellent functional outcome (OR = 1.20, and 95% CI = 1.02-1.42). In the network meta-analysis, Tenecteplase 0.25 mg/kg produces significant results in early neurological improvement (OR = 1.52 [95% CI = 1.13-2.05], p-value = 0.01), functional outcomes (mRS 0-1 and 0-2) (OR = 1.19 [95% CI = 1.03-1.37], p-value = 0.02; OR = 1.21 [95% CI = 1.05-1.39], p-value = 0.01; respectively) and mortality (OR = 0.78 [95% CI = 0.64-0.96], p-value = 0.02) whereas Tenecteplase 0.40 mg/kg increases the chances of symptomatic intracranial hemorrhage (OR = 2.35 [95% CI = 1.19-4.64], p-value = 0.01). Conclusion: While not conclusive, our study lends evidence to 0.25 mg/kg Tenecteplase dose for ischemic stroke treatment. Further randomized trials need to be done to validate this finding. Registration: International prospective register of systematic reviews (PROSPERO) - CRD42022339774URL: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=339774.

Antiplatelets or anticoagulants? Secondary prevention in cervical artery dissection: an updated meta-analysis.

BACKGROUND: Extracranial artery dissection involving either internal carotid artery or vertebral artery is a major cause of stroke in adults under 50 years of age. There is no conclusive evidence whether antiplatelets or anticoagulants are better suited in the treatment of extracranial artery dissection. OBJECTIVES: To determine whether antiplatelets or anticoagulants have advantage over the other in the treatment of extracranial artery dissection for secondary prevention of recurrent ischemic events or death. METHODS: Present meta-analysis followed Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement. Database search was done in Medline, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov from inception to May 2021 using pre-defined search strategy. Additional studies were identified from reference lists from included studies, reviews and previous meta-analyses. Outcome measures were ischaemic stroke, ischaemic stroke or transient ischaemic attack (TIA), and death. RESULTS: Two RCTs and 64 observational studies were included in the meta-analysis. While the outcome measures of stroke, stroke or TIA and death were numerically higher with antiplatelet use, there were no statistically significant differences between antiplatelets and anticoagulants. CONCLUSION: We found no significant difference between antiplatelet and anticoagulation treatment after extracranial artery dissection. The choice of treatment should be tailored to individual cases.

Internal cerebral vein asymmetry is an independent predictor of poor functional outcome in endovascular thrombectomy.

BACKGROUND: Endovascular thrombectomy (EVT) in large vessel occlusion (LVO) in anterior circulation acute ischaemic stroke (AIS) results in good functional outcomes in only approximately 60% of the patients. Internal cerebral veins (ICVs) are easily visible, with a consistent midline location, and are linked to stroke outcomes. We hypothesize that ICV asymmetry on multiphasic CT angiogram (mCTA) can be an adjunctive predictor for poor functional outcomes. METHODS: We studied consecutive AIS patients from 2017 to 2019 with anterior circulation LVO treated with EVT regardless of intravenous thrombolysis. Asymmetrical ICV was defined as the presence of hypodensity (less opacification) on the ipsilateral occlusion side as compared with the contralateral side. The primary outcome was modified Rankin Score (mRS) score at 3 months. Secondary outcomes were good recanalization (modified Thrombolysis In Cerebral Infarction (mTICI) 2b-3), symptomatic hemorrhage, and mortality. RESULTS: A total of 185 patients were included with a median age of 70 years (IQR 59-77); 87 patients (47%) were female. 82 patients (44.3%) achieved good functional outcomes (mRS 0-2) at 3 months. On multivariate analysis, National Institutes of Health Stroke Scale (NIHSS) (OR 1.076, 95% CI 1.015 to 1.140; p<0.013), poor collateral score (OR 0.285, 95% CI 0.162 to 0.501; p<0.001), asymmetrical ICV on the peak venous phase (OR 2.47, 95% CI 1.115 to 5.471; p<0.026), and late venous phase of the mCTA (OR 2.642, 95% CI 1.161 to 6.016; p<0.021) were independent risks factors of poor outcomes. CONCLUSION: ICV asymmetry is a novel radiological sign which is independently associated with poor functional outcomes in EVT, even after correction for collateral circulation. Further studies are needed to validate this finding.

Long-term outcomes of ischaemic stroke patients with diabetes in a multi-ethnic cohort in Singapore.

INTRODUCTION: Diabetes increases the risk of ischaemic stroke especially among Asians. This study aims to investigate contemporaneous long-term cardiovascular outcomes of ischaemic stroke patients with diabetes in a multi-ethnic Asian cohort. METHODS: Consecutive patients with ischaemic stroke were recruited from the National University Hospital, Singapore. Data on age, gender, ethnicity, risk factors (including diabetes status and body mass index [BMI]), stroke severity and mechanisms were collected. These patients were followed up until the day of the first cardiovascular event or July 2016, whichever was earlier. The primary endpoint was the time from enrolment to the first occurrence of a composite of cerebrovascular and coronary artery events. RESULTS: Between July 2011 and December 2013, 720 patients (mean age 60.6 years, 71% men, 43% with diabetes, median National Institute Health Stroke Severity scale 2) were enrolled and followed up. A total of 175 cardiovascular events occurred during a median follow-up of 3.25 years (6.90 events per 1,000 person-month), comprising 133 cerebrovascular and 42 coronary artery events. The adjusted hazard ratio of diabetes was 1.50 (95% CI 1.08-2.10). In a multivariable Cox proportional hazards model, Malay and Indian ethnicities, BMI <23kg/m2 and a prior diagnosis of diabetes were identified as independent predictors of recurrent cardiovascular events. CONCLUSION: Our study provides quantitative data on the event rates of ischaemic stroke patients with diabetes. These findings provide insights on stroke predictors in a multi-ethnic Asian population, which may have implications in the design of future interventional studies.