Polypharmacy, functional outcome and treatment effect of intravenous alteplase for acute ischaemic stroke

Introduction To assess the association between 24 h blood pressure variability (BPV) on functional outcome and treatment effect of intravenous alteplase in acute ischaemic stroke. Patients and methods In all patients with acute ischaemic stroke of unknown onset randomised in the WAKE-UP (Efficacy and Safety of magnetic resonance imaging [MRI]-based Thrombolysis in Wake-Up Stroke) trial, blood pressure (BP) was measured before randomisation and after initiation of treatment at regular intervals up to 24 hours. Individual BPV was measured by coefficient of variation (CV) of all BP values. Primary outcome measure was favourable outcome defined by a modified Rankin Scale (mRS) score 0 or 1 at 90 days after stroke. Results BP measurements were available for 498 of 503 patients randomised (177 women [35.5%], mean age [SD] of 65.2 [11.5] years). Systolic BPV was not associated with the treatment effect of thrombolysis (test for interaction, p = 0.46). The adjusted odds ratio (aOR) for favourable outcome with alteplase, adjusted for age, stroke severity and baseline BP on admission, did not show an association across the quintiles of increasing systolic BPV with an aOR 1.89 (95% confidence interval [CI], 0.76–4.70) in the lowest quintile to aOR 1.05 (95% CI, 0.43–2.56) in the highest quintile. Higher mean systolic BP was associated with a smaller treatment effect of thrombolysis with a significant interaction (p = 0.033). The aOR for favourable outcome with alteplase decreased with quintiles of increasing mean systolic BP from aOR 3.16 (95% CI, 1.26–7.93) in the lowest quintile to aOR 0.84 (95% CI, 0.34–2.10) in in the highest quintile. Conclusions There was a significant interaction between mean systolic BP and treatment effect of thrombolysis with higher mean systolic BP being associated with poorer outcome. BPV was not associated with outcome after thrombolysis. ClinicalTrials.gov identifier NCT01525290.

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Efficacy and safety of butylphthalide for patients who had acute ischaemic stroke receiving intravenous thrombolysis or endovascular treatment (BAST trial): study protocol for a randomised placebo-controlled trial

BMJ Open ◽

10.1136/bmjopen-2020-045559 ◽

2021 ◽

Vol 11 (5) ◽

pp. e045559

Author(s):

Xuelei Zhang ◽

Anxin Wang ◽

Jing Yu Zhang ◽

Baixue Jia ◽

Xiaochuan Huo ◽

...

Keyword(s):

Ischaemic Stroke ◽

Endovascular Treatment ◽

Functional Outcome ◽

Acute Ischaemic Stroke ◽

Controlled Trial ◽

Intravenous Thrombolysis ◽

Serious Adverse Events ◽

Double Blind ◽

Ischaemic Injury ◽

Study Results

IntroductionAs a neuroprotective medication, butylphthalide (NBP) may help protect against cerebral ischaemic injury. However, evidence on whether NBP influences the outcomes of patients who had acute ischaemic stroke who are receiving revascularisation treatment is limited. This study aims to evaluate whether additional NBP therapy can improve the functional outcome of patients who receive intravenous recombinant tissue plasminogen activator and/or endovascular treatment (EVT).Methods and analysisThe study will be a randomised, double-blind, placebo-controlled, multiple-centre, parallel group trial. The sample size is estimated at 1200 patients. Eligible patients will be randomised at a 1:1 ratio to receive either NBP or placebo daily for 90 days, which will include 14 days of injections and 76 days of capsules. The first use of NBP/placebo will be started within 6 hours of onset of ischaemic stroke. The primary outcome is the functional outcome as assessed by the 90-day modified Rankin Scale, adjusted for baseline scores on the National Institutes of Health Stroke Scale. The primary safety outcome is the percentage of serious adverse events during the 90 days of treatment. This trial will determine whether NBP medication benefits patients who had acute ischaemic stroke who receive intravenous thrombolysis or EVT.Ethics and disseminationThe protocol was written according to the general ethical guidelines of the Declaration of Helsinki and approved by the Institutional Review Board/Ethics Committee of Beijing Tiantan Hospital, Capital Medical University with approval number KY 2018-003-02. Ethics committees of all participating sites have approved the study . Results of the study will be published in peer-reviewed scientific journals and shared in scientific presentations.Trial registration numberNCT03539445.

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Contrast extravasation and outcome of endovascular therapy in acute ischaemic stroke: a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2020-044917 ◽

2021 ◽

Vol 11 (7) ◽

pp. e044917

Author(s):

Tao Xu ◽

You Wang ◽

Jinxian Yuan ◽

Yangmei Chen ◽

Haiyan Luo

Keyword(s):

Systematic Review ◽

Ischaemic Stroke ◽

Functional Outcome ◽

Endovascular Therapy ◽

Acute Ischaemic Stroke ◽

Data Extraction ◽

Meta Analysis ◽

Poor Functional Outcome ◽

Eligibility Criteria ◽

Contrast Extravasation

ObjectiveContrast extravasation (CE) after endovascular therapy (EVT) is commonly present in acute ischaemic stroke (AIS) patients. Substantial uncertainties remain about the relationship between CE and the outcomes of EVT in patients with AIS. Therefore, we aimed to evaluate this association.DesignA systematic review and meta-analysis of published studies were performed.Data sourceWe systematically searched the Medline and Embase databases for relevant clinical studies. The last literature search in databases was performed in June 2020.Eligibility criteria for study selectionWe included studies exploring the associations between CE and the outcomes of EVT in patients with AIS undergoing EVT.Data extraction and synthesisTwo reviewers extracted relevant information and data from each article independently. We pooled ORs with CIs using a random-effects meta-analysis to calculate the associations between CE and outcomes of EVT. The magnitude of heterogeneity between estimates was quantified with the I2 statistic with 95% CIs.ResultsFifteen observational studies that enrolled 1897 patients were included. Patients with CE had higher risks of poor functional outcome at discharge (2.38, 95% CI 1.45 to 3.89 p=0.001; n=545) and poor functional outcome at 90 days (OR 2.16, 95% CI 1.20 to 3.90; n=1194). We found no association between CE and in-hospital mortality (OR 0.95, 95% CI 0.27 to 3.30; n=376) or 90-day mortality (OR 1.38, 95% CI 0.81 to 2.36; n=697) after EVT. Moreover, CE was associated with higher risks of post-EVT intracranial haemorrhage (ICH) (OR 6.68, 95% CI 3.51 to 12.70; n=1721) and symptomatic ICH (OR 3.26, 95% CI 1.97 to 5.40; n=1092).ConclusionsThis systematic review and meta-analysis indicates that in patients with AIS undergoing EVT, CE is associated with higher risks of unfavourable functional outcomes and ICH. Thus, we should pay more attention to CE in patients with AIS undergoing EVT.

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Serum 25-hydroxyvitamin D predicts the short-term outcomes of Chinese patients with acute ischaemic stroke

Clinical Science ◽

10.1042/cs20130284 ◽

2013 ◽

Vol 126 (5) ◽

pp. 339-346 ◽

Cited By ~ 56

Author(s):

Wen-Jun Tu ◽

Sheng-Jie Zhao ◽

Dong-Jiang Xu ◽

Hui Chen

Keyword(s):

Ischaemic Stroke ◽

Functional Outcome ◽

Prognostic Marker ◽

Acute Ischaemic Stroke ◽

Chinese Patients ◽

Short Term ◽

Hydroxyvitamin D ◽

Independent Prognostic Marker ◽

Vitamin D Levels ◽

25 Hydroxyvitamin D

Low vitamin D levels have been reported to contribute to the risk of cardiovascular events and mortality, especially stroke. In the present study we therefore evaluated the short-term prognostic value of serum 25(OH)D (25-hydroxyvitamin D) in Chinese patients with AIS (acute ischaemic stroke). From February 2010 to September 2012, consecutive stroke patients admitted to the emergency department at two hospitals in Beijing, China were identified. Clinical information was collected, and the serum concentration of 25(OH)D and NIHSS (National Institutes of Health Stroke Scale) were measured at the time of admission. Short-term functional outcome was measured using a modified Rankin Scale (mRS) at 90 days after admission. Multivariate analyses were performed using logistic regression models. During the inclusion period, 231 patients were diagnosed as having AIS, and 220 completed follow-up. The median serum 25(OH)D level was significantly lower in patients with AIS compared with normal controls [14.2 (10.2–18.9) ng/ml compared with 17.9 (12.5–22.9) ng/ml; P<0.001; values are medians (interquartile range)]. 25(OH)D was an independent prognostic marker of short-term functional outcome and death {0.79 (0.73–0.85) and 0.70 (0.50–0.98) respectively [values are odds rations (95% confidence intervals)]; P<0.01 for both, adjusted for NHISS, other predictors and vascular risk factors} in patients with AIS. In ROC (receiver operating characteristic) curve analysis, the prognostic accuracy of 25(OH)D was higher compared with all of the other serum predictors and was in the range of NIHSS score. In conclusion, these findings suggest that 25(OH)D is an independent prognostic marker for death and functional outcome within 90 days in Chinese patients with AIS even after adjusting for possible confounding factors

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STUDY OF SERUM ALBUMIN AS A PREDICTOR OF SHORT-TERM FUNCTIONAL OUTCOME IN ACUTE ISCHAEMIC STROKE

Journal of Evolution of Medical and Dental Sciences ◽

10.14260/jemds/2017/637 ◽

2017 ◽

Vol 6 (36) ◽

pp. 2957-2962

Author(s):

Reeta James ◽

Jog Antony ◽

Sreelakshmi Sreedhar ◽

Rohit Mathew ◽

Adarsh Surendran

Keyword(s):

Serum Albumin ◽

Ischaemic Stroke ◽

Functional Outcome ◽

Acute Ischaemic Stroke ◽

Short Term

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Association between metabolic syndrome and functional outcome in patients with acute ischaemic stroke

European Journal of Neurology ◽

10.1111/ene.12128 ◽

2013 ◽

Vol 21 (1) ◽

pp. 177-179 ◽

Cited By ~ 7

Author(s):

M. Y. Oh ◽

S. B. Ko ◽

S. H. Lee ◽

C. Kim ◽

W. S. Ryu ◽

...

Keyword(s):

Metabolic Syndrome ◽

Ischaemic Stroke ◽

Functional Outcome ◽

Acute Ischaemic Stroke

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Developing a multivariable prediction model for functional outcome after reperfusion therapy for acute ischaemic stroke: study protocol for the Targeting Optimal Thrombolysis Outcomes (TOTO) multicentre cohort study

BMJ Open ◽

10.1136/bmjopen-2020-038180 ◽

2020 ◽

Vol 10 (4) ◽

pp. e038180 ◽

Cited By ~ 1

Author(s):

Elizabeth Holliday ◽

Thomas Lillicrap ◽

Timothy Kleinig ◽

Philip M C Choi ◽

Jane Maguire ◽

...

Keyword(s):

Cohort Study ◽

Ischaemic Stroke ◽

Functional Outcome ◽

Acute Ischaemic Stroke ◽

Significant Risk ◽

Intravenous Thrombolysis ◽

Reperfusion Therapy ◽

Stroke Severity ◽

Local Health ◽

Predictive Algorithms

IntroductionIntravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) is the only approved pharmacological reperfusion therapy for acute ischaemic stroke. Despite population benefit, IVT is not equally effective in all patients, nor is it without significant risk. Uncertain treatment outcome prediction complicates patient treatment selection. This study will develop and validate predictive algorithms for IVT response, using clinical, radiological and blood-based biomarker measures. A secondary objective is to develop predictive algorithms for endovascular thrombectomy (EVT), which has been proven as an effective reperfusion therapy since study inception.Methods and analysisThe Targeting Optimal Thrombolysis Outcomes Study is a multicenter prospective cohort study of ischaemic stroke patients treated at participating Australian Stroke Centres with IVT and/or EVT. Patients undergo neuroimaging using multimodal CT or MRI at baseline with repeat neuroimaging 24 hours post-treatment. Baseline and follow-up blood samples are provided for research use. The primary outcome is good functional outcome at 90 days poststroke, defined as a modified Rankin Scale (mRS) Score of 0–2. Secondary outcomes are reperfusion, recanalisation, infarct core growth, change in stroke severity, poor functional outcome, excellent functional outcome and ordinal mRS at 90 days. Primary predictive models will be developed and validated in patients treated only with rt-PA. Models will be built using regression methods and include clinical variables, radiological measures from multimodal neuroimaging and blood-based biomarkers measured by mass spectrometry. Predictive accuracy will be quantified using c-statistics and R2. In secondary analyses, models will be developed in patients treated using EVT, with or without prior IVT, reflecting practice changes since original study design.Ethics and disseminationPatients, or relatives when patients could not consent, provide written informed consent to participate. This study received approval from the Hunter New England Local Health District Human Research Ethics Committee (reference 14/10/15/4.02). Findings will be disseminated via peer-reviewed publications and conference presentations.

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Endovascular treatment of acute ischaemic stroke in octogenarians and nonagenarians compared with younger patients

The Neuroradiology Journal ◽

10.1177/1971400919840847 ◽

2019 ◽

Vol 32 (4) ◽

pp. 303-308 ◽

Cited By ~ 2

Author(s):

Yasuhiro Kawabata ◽

Norio Nakajima ◽

Hidenori Miyake ◽

Shunichi Fukuda ◽

Tetsuya Tsukahara

Keyword(s):

Ischaemic Stroke ◽

Functional Outcome ◽

Scale Score ◽

Endovascular Therapy ◽

Acute Ischaemic Stroke ◽

Intravenous Thrombolysis ◽

Favourable Outcome ◽

Modified Rankin Scale ◽

Very Elderly ◽

Younger Patients

Purpose: Endovascular therapy for emergent large vessel occlusion has been established as the standard approach for acute ischaemic stroke. However, the effectiveness and safety of endovascular therapy in the very elderly population has not been proved. Objective: To determine the safety and effectiveness of endovascular therapy in octogenarians and nonagenarians. Methods: We retrospectively reviewed all patients who underwent endovascular therapy at two stroke centres between April 2012 and July 2018. Functional outcome was assessed using the modified Rankin scale at 90 days after stroke or at discharge. A favourable outcome was defined as a modified Rankin scale score of 0–2 or not worsening of the modified Rankin scale score before stroke. Outcome was compared between younger patients (aged 46–79 years, n = 40) and octogenarians and nonagenarians (aged 80–97 years, n = 19). Results: Octogenarian and nonagenarian patients had pre-stroke functional deficit (modified Rankin scale score >1) more frequently than younger patients (57.9% vs. 20.0%, respectively, P = 0.0059). No difference was observed between very elderly and younger patients in the rate of successful reperfusion (89.5% vs. 67.5%, respectively, P = 0.11), favourable functional outcome (47.4% vs. 45.0%, respectively, P = 1.00) and mortality (21.1% vs. 27.5%, respectively, P = 1.00). On multiple regression analysis, successful reperfusion, concomitant use of intravenous thrombolysis, and out-of-hospital onset were independent predictors of favourable outcome ( P = 0.0003, 0.015 and 0.028, respectively). Conclusions: Successful reperfusion, concomitant use of intravenous thrombolysis, and out-of-hospital onset were clinical predictors of favourable outcome. However, we did not observe an age-dependent effect of clinical outcome after endovascular therapy.

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The natural tissue plasminogen activator inhibitor neuroserpin and acute ischaemic stroke outcome

Thrombosis and Haemostasis ◽

10.1160/th10-09-0621 ◽

2011 ◽

Vol 105 (03) ◽

pp. 421-429 ◽

Cited By ~ 10

Author(s):

Tomás Sobrino ◽

Elena Miranda ◽

David Brea ◽

Natalia Pérez de la Ossa ◽

Miguel Blanco ◽

...

Keyword(s):

Ischaemic Stroke ◽

Functional Outcome ◽

Plasminogen Activator ◽

Tissue Plasminogen Activator ◽

Acute Ischaemic Stroke ◽

High Serum ◽

Favourable Outcome ◽

Neuroprotective Effects ◽

Good Functional Outcome ◽

Tissue Plasminogen

SummaryNeuroserpin is a brain-derived natural inhibitor of tissue plasminogen activator (tPA) that has shown neuroprotective effects in animal models of brain ischaemia. Our aim was to investigate the association of neuroserpin levels in blood with functional outcome in patients with acute ischaemic stroke. Due to the potential effect of tPA treatment interfering on neuroserpin levels, we studied two different cohorts: 129 patients not treated with tPA and 80 patients treated with intravenous tPA within 3 hours (h) from symptoms onset. Neuroserpin levels were measured by ELISA. Good functional outcome at three months was defined as Rankin scale score ≤2. In the two cohorts, serum neuroserpin levels on admission were significantly higher than at 24 h, 72 h and in healthy subjects. In non tPA-treated patients, neuroserpin levels decrease at 24 h, but not levels at baseline, were associated with good outcome (for each quartile decrease, adjusted odds ratio [OR] 15.0; 95% confidence interval [CI], 3.5 to 66). In the tPA-treated cohort, high neuroserpin levels before tPA bolus had the stronger effect on favourable outcome (for each quartile, OR 13.5; 95%CI, 3.9 to 47). Furthermore, for each quartile in neuroserpin levels before tPA bolus there was a 80% (95%CI, 48 to 92) reduction in the probability of subsequent parenchymal haematoma. In summary, high serum neuroserpin levels before intravenous tPA and neuroserpin levels decrease at 24 h after ischaemic stroke, independently of tPA treatment, are associated with good functional outcome. These findings support the concept that neuroserpin might play an important role during cerebral ischaemia.

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Sedation versus general anaesthesia in endovascular therapy for anterior circulation acute ischaemic stroke: the multicentre randomised controlled AMETIS trial study protocol

BMJ Open ◽

10.1136/bmjopen-2018-027561 ◽

2019 ◽

Vol 9 (9) ◽

pp. e027561 ◽

Cited By ~ 3

Author(s):

Russell Chabanne ◽

Charlotte Fernandez-Canal ◽

Vincent Degos ◽

Anne-Claire Lukaszewicz ◽

Lionel Velly ◽

...

Keyword(s):

Ischaemic Stroke ◽

Functional Outcome ◽

General Anaesthesia ◽

Endovascular Therapy ◽

Acute Ischaemic Stroke ◽

Intravenous Thrombolysis ◽

Functional Independence ◽

Acute Pulmonary Oedema ◽

Anterior Circulation ◽

Randomised Controlled

IntroductionEndovascular thrombectomy is the standard of care for anterior circulation acute ischaemic stroke (AIS) secondary to emergent large vessel occlusion in patients who qualify. General anaesthesia (GA) or conscious sedation (CS) is usually required to ensure patient comfort and avoid agitation and movement during thrombectomy. However, the question of whether the use of GA or CS might influence functional outcome remains debated. Indeed, conflicting results exist between observational studies with better outcomes associated with CS and small monocentric randomised controlled trials favouring GA. Therefore, we aim to evaluate the effect of CS versus GA on functional outcome and periprocedural complications in endovascular mechanical thrombectomy for anterior circulation AIS.Methods and analysisAnesthesia Management in Endovascular Therapy for Ischemic Stroke (AMETIS) trial is an investigator initiated, multicentre, prospective, randomised controlled, two-arm trial. AMETIS trial will randomise 270 patients with anterior circulation AIS in a 1:1 ratio, stratified by centre, National Institutes of Health Stroke Scale (≤15 or >15) and association of intravenous thrombolysis or not to receive either CS or GA. The primary outcome is a composite of functional independence at 3 months and absence of perioperative complication occurring by day 7 after endovascular therapy for anterior circulation AIS. Functional independence is defined as a modified Rankin Scale score of 0–2 by day 90. Perioperative complications are defined as intervention-associated arterial perforation or dissection, pneumonia or myocardial infarction or cardiogenic acute pulmonary oedema or malignant stroke evolution occurring by day 7.Ethics and disseminationThe AMETIS trial was approved by an independent ethics committee. Study began in august 2017. Results will be published in an international peer-reviewed medical journal.Trial registration numberNCT03229148.

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