Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials

Quality of life after stroke: Evaluation of the Greek SAQOL-39g

Background/Aims: Stroke and aphasia rehabilitation aims to improve people’s quality of life. Yet, scales for measuring health-related quality of life in stroke typically exclude people with aphasia. They are also primarily available in English. An exception is the Stroke and Aphasia Quality of Life scale (SAQOL-39g). This scale has been tested with people with aphasia; it has been adapted for use in many countries including Greece. The aim of this study was to examine the psychometric properties of the Greek SAQOL-39g. Methods: An interview-based psychometric study was carried out. Participants completed: receptive sub-tests of Frenchay Aphasia Screening Test, Greek SAQOL-39g, General Health Questionnaire-12, Frenchay Activities Index, Montreal Cognitive Assessment and Barthel Index. Results: 86 people took part; 26 provided test-retest reliability data. The Greek SAQOL-39g demonstrated excellent acceptability (minimal missing data; no floor/ceiling effects), test-retest reliability (ICC= 0.96 scale, 0.83-0.99 domains) and internal consistency (Cronbach’s alpha 0.96 scale, 0.92-0.96 domains). There was strong evidence for convergent (r=0.53-0.80 scale; 0.54-0.89 domains) and discriminant validity (r=0.52 scale; 0.04-0.48 domains). Conclusion: The Greek SAQOL-39g is a valid and reliable scale. It is a promising measure for use in stroke and aphasia treatment prioritization, outcome measurement and service evaluation

Oral Anticoagulants in the Oldest Old with Recent Stroke and Atrial Fibrillation

OBJECTIVE: To investigate the safety and effectiveness of direct oral anticoagulants (DOAC) versus vitamin-K-antagonists (VKA) after recent stroke in patients with atrial fibrillation (AF) aged ≥85 years. METHODS: Individual patient data analysis from 7 prospective stroke cohorts. We compared DOAC versus VKA treatment among patients with AF and recent stroke (<3 months) aged ≥85 versus <85 years. Primary outcome was the composite of recurrent stroke, intracranial hemorrhage (ICH) and all-cause death. We used simple, adjusted and weighted Cox regression to account for confounders. We calculated the net benefit of DOAC versus VKA by balancing stroke reduction against the weighted ICH risk. RESULTS: In total, 5,984 of 6,267 (95.5%) patients were eligible for analysis. Of those, 1,380 (23%) were aged ≥85 years and 3,688 (62%) received a DOAC. During 6,874 patient-years follow-up, the impact of anticoagulant type (DOAC versus VKA) on the hazard for the composite outcome did not differ between patients aged ≥85 (HR≥85y =0.65, 95%-CI [0.52, 0.81]) and <85 years (HR<85y =0.79, 95%-CI [0.66, 0.95]) in simple (pinteraction =0.129), adjusted (pinteraction =0.094) or weighted (pinteraction =0.512) models. Analyses on recurrent stroke, ICH and death separately were consistent with the primary analysis, as were sensitivity analyses using age dichotomized at 90 years and as a continuous variable. DOAC had a similar net clinical benefit in patients aged ≥85 (+1.73 to +2.66) and <85 years (+1.90 to +3.36 events/100 patient-years for ICH-weights 1.5 to 3.1). INTERPRETATION: The favorable profile of DOAC over VKA in patients with AF and recent stroke was maintained in the oldest old

Ischemic Stroke despite Oral Anticoagulant Therapy in Patients with Atrial Fibrillation

OBJECTIVE It is not known whether patients with atrial fibrillation (AF) with ischemic stroke despite oral anticoagulant therapy are at increased risk for further recurrent strokes or how ongoing secondary prevention should be managed. METHODS We conducted an individual patient data pooled analysis of 7 prospective cohort studies that recruited patients with AF and recent cerebral ischemia. We compared patients taking oral anticoagulants (vitamin K antagonists [VKA] or direct oral anticoagulants [DOAC]) prior to index event (OACprior) with those without prior oral anticoagulation (OACnaive). We further compared those who changed the type (ie, from VKA or DOAC, vice versa, or DOAC to DOAC) of anticoagulation (OACchanged) with those who continued the same anticoagulation as secondary prevention (OACunchanged). Time to recurrent acute ischemic stroke (AIS) was analyzed using multivariate competing risk Fine–Gray models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS We included 5,413 patients (median age = 78 years [interquartile range (IQR) = 71–84 years]; 5,136 [96.7%] had ischemic stroke as the index event, median National Institutes of Health Stroke Scale on admission = 6 [IQR = 2–12]). The median CHA2DS2‐Vasc score (congestive heart failure, hypertension, age≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65–74 years, sex category) was 5 (IQR = 4–6) and was similar for OACprior (n = 1,195) and OACnaive (n = 4,119, p = 0.103). During 6,128 patient‐years of follow‐up, 289 patients had AIS (4.7% per year, 95% CI = 4.2–5.3%). OACprior was associated with an increased risk of AIS (HR = 1.6, 95% CI = 1.2–2.3, p = 0.005). OACchanged (n = 307) was not associated with decreased risk of AIS (HR = 1.2, 95% CI = 0.7–2.1, p = 0.415) compared with OACunchanged (n = 585). INTERPRETATION Patients with AF who have an ischemic stroke despite previous oral anticoagulation are at a higher risk for recurrent ischemic stroke despite a CHA2DS2‐Vasc score similar to those without prior oral anticoagulation. Better prevention strategies are needed for this high‐risk patient group. ANN NEUROL 202

Serum magnesium and calcium levels in relation to ischemic stroke : Mendelian randomization study

ObjectiveTo determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach.MethodsAnalyses were conducted using summary statistics data for 13 single-nucleotide polymorphisms robustly associated with serum magnesium (n = 6) or serum calcium (n = 7) concentrations. The corresponding data for ischemic stroke were obtained from the MEGASTROKE consortium (34,217 cases and 404,630 noncases).ResultsIn standard mendelian randomization analysis, the odds ratios for each 0.1 mmol/L (about 1 SD) increase in genetically predicted serum magnesium concentrations were 0.78 (95% confidence interval [CI] 0.69-0.89; p = 1.3 × 10-4) for all ischemic stroke, 0.63 (95% CI 0.50-0.80; p = 1.6 × 10-4) for cardioembolic stroke, and 0.60 (95% CI 0.44-0.82; p = 0.001) for large artery stroke; there was no association with small vessel stroke (odds ratio 0.90, 95% CI 0.67-1.20; p = 0.46). Only the association with cardioembolic stroke was robust in sensitivity analyses. There was no association of genetically predicted serum calcium concentrations with all ischemic stroke (per 0.5 mg/dL [about 1 SD] increase in serum calcium: odds ratio 1.03, 95% CI 0.88-1.21) or with any subtype.ConclusionsThis study found that genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke but found no significant association of genetically higher serum calcium concentrations with any ischemic stroke subtype

Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomised controlled trial

Background: Current evidence supports the use of intravenous thrombolysis with alteplase in patients with wake-up stroke selected with MRI or perfusion imaging and is recommended in clinical guidelines. However, access to advanced imaging techniques is often scarce. We aimed to determine whether thrombolytic treatment with intravenous tenecteplase given within 4·5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT. Methods: TWIST was an investigator-initiated, multicentre, open-label, randomised controlled trial with blinded endpoint assessment, conducted at 77 hospitals in ten countries. We included patients aged 18 years or older with acute ischaemic stroke symptoms upon awakening, limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher or aphasia, a non-contrast CT examination of the head, and the ability to receive tenecteplase within 4·5 h of awakening. Patients were randomly assigned (1:1) to either a single intravenous bolus of tenecteplase 0·25 mg per kg of bodyweight (maximum 25 mg) or control (no thrombolysis) using a central, web-based, computer-generated randomisation schedule. Trained research personnel, who conducted telephone interviews at 90 days (follow-up), were masked to treatment allocation. Clinical assessments were performed on day 1 (at baseline) and day 7 of hospital admission (or at discharge, whichever occurred first). The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days and analysed using ordinal logistic regression in the intention-to-treat population. This trial is registered with EudraCT (2014–000096–80), ClinicalTrials.gov (NCT03181360), and ISRCTN (10601890). Findings: From June 12, 2017, to Sept 30, 2021, 578 of the required 600 patients were enrolled (288 randomly assigned to the tenecteplase group and 290 to the control group [intention-to-treat population]). The median age of participants was 73·7 years (IQR 65·9–81·1). 332 (57%) of 578 participants were male and 246 (43%) were female. Treatment with tenecteplase was not associated with better functional outcome, according to mRS score at 90 days (adjusted OR 1·18, 95% CI 0·88–1·58; p=0·27). Mortality at 90 days did not significantly differ between treatment groups (28 [10%] patients in the tenecteplase group and 23 [8%] in the control group; adjusted HR 1·29, 95% CI 0·74–2·26; p=0·37). Symptomatic intracranial haemorrhage occurred in six (2%) patients in the tenecteplase group versus three (1%) in the control group (adjusted OR 2·17, 95% CI 0·53–8·87; p=0·28), whereas any intracranial haemorrhage occurred in 33 (11%) versus 30 (10%) patients (adjusted OR 1·14, 0·67–1·94; p=0·64). Interpretation: In patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days. The number of symptomatic haemorrhages and any intracranial haemorrhages in both treatment groups was similar to findings from previous trials of wake-up stroke patients selected using advanced imaging. Current evidence does not support treatment with tenecteplase in patients selected with non-contrast CT. Funding: Norwegian Clinical Research Therapy in the Specialist Health Services Programme, the Swiss Heart Foundation, the British Heart Foundation, and the Norwegian National Association for Public Health

A Delphi Consensus Study

Funding Information: We sincerely thank all the experts who participated in this Delphi study for their time and for sharing their expertise. All Delphi experts qualify for authorship based on the fact that they were involved in data collection and all critically appraised the final manuscript for important intellectual content. See Appendix B for the names of the Delphi experts. Publisher Copyright: © 2021 The AuthorsObjective: No dedicated studies have been performed on the optimal management of patients with an acute stroke related to carotid intervention nor is there a solid recommendation given in the European Society for Vascular Surgery guideline. By implementation of an international expert Delphi panel, this study aimed to obtain expert consensus on the optimal management of in hospital stroke occurring during or following CEA and to provide a practical treatment decision tree. Methods: A four round Delphi consensus study was performed including 31 experts. The aim of the first round was to investigate whether the conceptual model indicating the traditional division between intra- and post-procedural stroke in six phases was appropriate, and to identify relevant clinical responses during these six phases. In rounds 2, 3, and 4, the aim was to obtain consensus on the optimal response to stroke in each predefined setting. Consensus was reached in rounds 1, 3, and 4 when ≥ 70% of experts agreed on the preferred clinical response and in round 2 based on a Likert scale when a median of 7 – 9 (most adequate response) was given, IQR ≤ 2. Results: The experts agreed (> 80%) on the use of the conceptual model. Stroke laterality and type of anaesthesia were included in the treatment algorithm. Consensus was reached in 17 of 21 scenarios (> 80%). Perform diagnostics first for a contralateral stroke in any phase, and for an ipsilateral stroke during cross clamping, or apparent stroke after leaving the operation room. For an ipsilateral stroke during the wake up phase, no formal consensus was achieved, but 65% of the experts would perform diagnostics first. A CT brain combined with a CTA or duplex ultrasound of the carotid arteries should be performed. For an ipsilateral intra-operative stroke after flow restoration, the carotid artery should be re-explored immediately (75%). Conclusion: In patients having a stroke following carotid endarterectomy, expedited diagnostics should be performed initially in most phases. In patients who experience an ipsilateral intra-operative stroke following carotid clamp release, immediate re-exploration of the index carotid artery is recommended.publishersversionpublishe

Recurrent Ischemic Stroke and Bleeding in Patients With Atrial Fibrillation Who Suffered an Acute Stroke While on Treatment With Nonvitamin K Antagonist Oral Anticoagulants: The RENO-EXTEND Study

Background: In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain. Methods: This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment. Results: After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA2DS2-VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0–1.3] for each point increase; P=0.05) and hypertension (OR, 2.3 [95% CI, 1.0–5.1]; P=0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0–1.2] for each year increase; P=0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4–14.2]; P=0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4–5.5]; P=0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8–1.7]). Conclusions: Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding

Status Update and Interim Results from the Asymptomatic Carotid Surgery Trial-2 (ACST-2)

Objectives: ACST-2 is currently the largest trial ever conducted to compare carotid artery stenting (CAS) with carotid endarterectomy (CEA) in patients with severe asymptomatic carotid stenosis requiring revascularization. Methods: Patients are entered into ACST-2 when revascularization is felt to be clearly indicated, when CEA and CAS are both possible, but where there is substantial uncertainty as to which is most appropriate. Trial surgeons and interventionalists are expected to use their usual techniques and CE-approved devices. We report baseline characteristics and blinded combined interim results for 30-day mortality and major morbidity for 986 patients in the ongoing trial up to September 2012. Results: A total of 986 patients (687 men, 299 women), mean age 68.7 years (SD ± 8.1) were randomized equally to CEA or CAS. Most (96%) had ipsilateral stenosis of 70-99% (median 80%) with contralateral stenoses of 50-99% in 30% and contralateral occlusion in 8%. Patients were on appropriate medical treatment. For 691 patients undergoing intervention with at least 1-month follow-up and Rankin scoring at 6 months for any stroke, the overall serious cardiovascular event rate of periprocedural (within 30 days) disabling stroke, fatal myocardial infarction, and death at 30 days was 1.0%. Conclusions: Early ACST-2 results suggest contemporary carotid intervention for asymptomatic stenosis has a low risk of serious morbidity and mortality, on par with other recent trials. The trial continues to recruit, to monitor periprocedural events and all types of stroke, aiming to randomize up to 5,000 patients to determine any differential outcomes between interventions. Clinical trial: ISRCTN21144362. © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved