Insights from ARCOS-V's Transition to Remote Data Collection during the COVID-19 Pandemic: A Descriptive Study.

INTRODUCTION: The ARCOS-V study, an epidemiological study on stroke and transient ischaemic attack (TIA), faced the challenge of continuing data collection amidst the COVID-19 pandemic. This study aimed to describe the methodological changes and challenges encountered during the transition from paper-based methods to digital data collection for the ARCOS-V study and to provide insights into the potential of using digital tools to transform epidemiological research. METHODS: The study adapted to remote data collection using REDCap and Zoom, involving daily health record reviews, direct data entry by trained researchers, and remote follow-up assessments. The process was secured with encryption and role-based access controls. The transition period was analysed to evaluate the effectiveness and challenges of the new approach. RESULTS: The digital transition allowed for uninterrupted monitoring of stroke and TIA cases during lockdowns. Using REDCap and Zoom improved data reach, accuracy, and security. However, it also revealed issues such as the potential for systematic data entry errors and the need for robust security measures to protect sensitive health information. CONCLUSION: The ARCOS-V study's digital transformation exemplifies the resilience of epidemiological research in the face of a global crisis. The successful adaptation to digital data collection methods highlights the potential benefits of such tools, particularly as we enter a new age of artificial intelligence (AI).

Pre-hospital transdermal glyceryl trinitrate for transient ischaemic attack: Data from the RIGHT-2 trial.

BACKGROUND AND PURPOSE: Ambulance trials assessing interventions in suspected stroke patients will recruit patients with currently active symptoms that will resolve into transient ischaemic attack (TIA). The safety and efficacy of glyceryl trinitrate (GTN) in the pre-specified subgroup of patients with TIA in the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke Trial 2 (RIGHT-2) was assessed. METHODS: RIGHT-2 was a pre-hospital-initiated multicentre randomized sham-controlled blinded-endpoint trial that randomized patients with presumed ultra-acute stroke within 4 h of symptom onset to transdermal GTN or sham. Final diagnosis was determined by site investigators. The primary outcome was a shift in modified Rankin Scale (mRS) scores at 90 days analysed using ordinal logistic regression reported as adjusted common odds ratio with 95% confidence intervals (CIs). Secondary outcomes included death or dependence (mRS >2). RESULTS: In all, 109 of 1149 (9.5%) patients had a final diagnosis of TIA (GTN 57, sham 52) with mean age 73 (SD 13) years, 19 (17.4%) had pre-morbid mRS >2, and onset to randomization was 80 min (interquartile range 49, 105). GTN lowered blood pressure by 7.4/5.2 mmHg compared with sham by hospital arrival. At day 90, GTN had no effect on shift in mRS scores (common odds ratio for increased dependence 1.47, 95% CI 0.70-3.11) but was associated with increased death or dependence (mRS >2): GTN 29 (51.8%) versus sham 23 (46.9%), odds ratio 3.86 (95% CI 1.09-13.59). CONCLUSIONS: Pre-hospital ultra-acute transdermal GTN did not improve overall functional outcome in patients with investigator-diagnosed TIA compared with sham treatment.

Two or More Ischaemic Events Within Seven Days Before Carotid Endarterectomy Increases the Risk of Peri-operative Stroke or Death.

OBJECTIVE: The aim of this study was to determine how many pre-operative ischaemic events occurring within a specific timeframe before carotid endarterectomy (CEA) are needed to increase the peri-operative 30 day risk of stroke or death. METHODS: This was a secondary exploratory analysis based on pooled data from three observational studies sourced from a single centre. Patients with recently symptomatic conventional ≥ 50% carotid stenosis were included. The principal analysis was limited to patients presenting with stroke or transient ischaemic attack (TIA). The primary outcome was 30 day risk of peri-operative stroke or death. Whether one, two, three, or four or more ipsilateral pre-operative ischaemic events within three, seven, 14, or 30 days before CEA were associated with the primary outcome was assessed. RESULTS: The study included 382 patients who underwent CEA with symptomatic conventional ≥ 50% carotid stenosis with stroke or TIA as the presenting event. Mean patient age ± standard deviation was 72 ± 7 years, 117 (30.6%) were female, and 5% were treated with dual antiplatelet therapy. The primary outcome occurred in 21 patients (5.5%). Two or more events within 7 days before CEA was the most discriminative definition of repeated events, with a 14.3% (8/56) risk of the primary outcome. Those who fell outside this definition of two or more events within seven days before CEA had a 4.0% (13/326; p = .006) risk of experiencing the primary outcome (adjusted odds ratio 4.1, 95% confidence interval 1.6 - 10.5). Several alternative definitions were assessed, but patients with two or more events within seven days before CEA and negative for these alternatives still had a > 10% risk of the primary outcome. CONCLUSION: Two or more ipsilateral ischaemic events within seven days before CEA is associated with an increased risk of peri-operative stroke or death in cases with symptomatic conventional ≥ 50% carotid stenosis and TIA or stroke as the presenting event. Studies assessing whether delayed or immediate CEA is preferable for this patient group are warranted.

Impact of European Stroke Organisation secondary prevention guideline for ischaemic stroke / transient ischaemic attack.

OBJECTIVES: We aimed to assess secondary prevention strategies after ischaemic stroke or transient ischaemic attack (TIA). MATERIALS AND METHODS: We investigated the impact of European Stroke Organisation (ESO) Guideline recommendations for secondary prevention on recurrent events among people with non-cardioembolic ischaemic stroke or TIA. We assessed the following interventions by survival analysis or modelling impacts from clinical trial data: two blood pressure (BP) drugs compared to one drug; LDL-cholesterol target <1.8 mmol/L; and pioglitazone therapy. Outcomes were mortality, major adverse cardiovascular events (MACE) and recurrent stroke or myocardial infarction (MI). RESULTS: We included 4,037 people admitted between 01/12/2015 to 31/12/2018: mean (SD) age 68.6 (12.9) years; 1984 (49.1 %) female and median (IQR) follow-up 2.2 (1.5-3.1) years. Prescription of two BP drugs was associated with reduced mortality in our sample of 2238 people with hypertension (HR 0.64, 95 %CI 0.51-0.81; P<0.001). We estimate an LDL-cholesterol target <1.8 mmol/L could reduce MACE incidence from 128 to 114 events (95 %CI 103-127) in our sample of 1024 people with LDL-cholesterol 1.8 mmol/L who were not already prescribed intensive lipid-lowering therapy over median (IQR) 2.2 (1.5-2.9) years follow-up (ARR 1.38 %, NNT 73). We estimate pioglitazone therapy could reduce incidence of recurrent stroke or MI from 192 to 169 events (95 %CI 156-185) in our sample of 1587 people with diabetes or insulin resistance over median (IQR) 2.4 (1.7-3.2) years follow-up (ARR 1.45 %, NNT 69). CONCLUSIONS: We estimate that implementing ESO guidelines in a Scottish population after ischaemic stroke or TIA would reduce mortality and recurrent cardiovascular events.

A systematic review of the incidence and outcomes of ICD-11 defined stroke.

BACKGROUND: The World Health Organisation has expanded the definition of stroke to include people with symptoms less than 24 h if they have evidence of stroke on neuroimaging. The impact is that people previously diagnosed as having a transient ischaemic attack (TIA) would now be considered to have had a stroke. This change will impact incidence and outcomes of stroke and increase eligibility for secondary prevention. We aimed to evaluate the new ICD-11 criteria retrospectively to previous TIA studies to understand the change in incidence and outcomes of this type of stroke. METHODS: We conducted a systematic review of observational studies of the incidence and outcomes of clinically defined TIA. We searched PubMed, EMBASE, and Google Scholar from inception to 23rd May 2023. Study quality was assessed using a risk of bias tool for prevalence studies. FINDINGS: Our review included 25 studies. The rate of scan positivity for stroke among those with clinically defined TIA was 24 %, (95 % CI, 16-33 %) but with high heterogeneity (I2 = 100 %, p <0.001). Sensitivity analyses provided evidence that heterogeneity could be explained by methodology and recruitment method. The scan positive rate when examining only studies at low risk of bias was substantially lower, at 13 % (95 % CI, 11-15 %, I2 = 0, p = 0.77). We estimate from population-based incidence studies that ICD-11 would result in an increase stroke incidence between 4.8 and 10.5 per 100,000 persons/year. Of those with DWI-MRI evidence of stroke, 6 % (95 % CI, 3-11 %) developed a recurrent stroke in the subsequent 90 days, but with substantial heterogeneity (I2 = 67 %, p = 0.02). CONCLUSION: The impact of the ICD-11 change in stroke definition on incidence and outcomes may have been overestimated by individual studies. Community-based stroke services with access to DWI MRI are likely to accurately diagnose greater numbers of people with mild ICD-11 stroke, increasing access to effective prevention.

Routine transthoracic echocardiography in ischaemic stroke or transient ischaemic attack of undetermined cause: a prospective multicentre study.

BACKGROUND: Guidelines recommend routine transthoracic echocardiography (TTE) after ischaemic stroke or transient ischaemic attack of undetermined cause; yet, only limited scientific evidence exists. Therefore, we aimed to determine in these patients the prevalence of TTE-detected major cardiac sources of embolism (CSE), which are abnormalities leading to therapeutic changes. METHODS: Six Dutch hospitals conducted a prospective observational study that enrolled patients with ischaemic stroke or transient ischaemic attack of undetermined cause. Patients underwent TTE after comprehensive diagnostic evaluation on stroke units, including blood chemistry, 12-lead electrocardiogram (ECG), ≥ 24 h continuous ECG monitoring, brain imaging and cervical artery imaging. Primary outcome measure was the proportion of patients with TTE-detected major CSE. RESULTS: From March 2018 to October 2020, 1084 patients, aged 66.6 ± 12.5 years, were enrolled; 456 (42.1%) patients were female and 869 (80.2%) had ischaemic stroke. TTE detected major CSE in only 11 (1.0%) patients. Ten (90.9%) of these patients also had major ECG abnormalities (previous infarction, major repolarisation abnormalities, or previously unknown left bundle branch block) that would have warranted TTE assessment regardless of stroke evaluation. Such ECG abnormalities were present in 11.1% of the total study population. A single patient (0.1%) showed a major CSE despite having no ECG abnormality. CONCLUSIONS: This multicentre cross-sectional study in patients who-after workup on contemporary stroke units-were diagnosed with ischaemic stroke or transient ischaemic attack of undetermined cause found TTE-detected major CSE in only 1% of all patients. Most of these patients also had major ECG abnormalities. These findings question the value of routine TTE assessment in this clinical setting.

Mortality in a Multiethnic Population Attending a One-Stop TIA Clinic.

INTRODUCTION: Studies indicate a 13-27% mortality rate following a transient ischaemic attack (TIA). However, outcomes following TIA/minor stroke since the introduction of rapid-access TIA clinics and prompt vascular risk factor intervention are not known. Specifically, there is paucity of data comparing outcomes between people who are diagnosed with an "acute cerebrovascular" (CV) event or an alternative non-cardiovascular diagnosis (non-CV) in a rapid-access TIA clinic. We aimed to assess the mortality in such a setting. METHODS: A retrospective observational study was undertaken at the Leicester rapid-access secondary care TIA clinic. Data included information collected at the first clinic visit (including comorbidities, and primary diagnosis, categorized as CV and non-CV) and the date of death for people dying during follow-up. RESULTS: 11,524 subjects were included with 33,164 years of follow-up data; 4,746 (41.2%) received a CV diagnosis. The median follow-up time was 2.75 years (interquartile range 1.36-4.32). The crude mortality rate was 37.3 (95% CI: 35.3-39.5) per 1,000 person-years (PTPY). The mortality rate was higher following a CV diagnosis (50.8 [47.2-54.7] PTPY) compared to a non-CV diagnosis (27.9 [25.7-30.4] PTPY), and for males, older people, those of white ethnicity, and people with orthostatic hypotension (OH). DISCUSSION: This study identified possible risk factors associated with a higher mortality in TIA clinic attendees, who may benefit from specific intervention. Future research should explore the underlying causes and the effect of specific targeted management strategies.

Atrial fibrillation, transient ischaemic attack and stroke in older people. A themed collection in age and ageing journal.

With an increase in the ageing population, there is a rise in the burden of cardiovascular disease. Age and Ageing have compiled collections of their key cardiovascular themed papers. The first Age and Ageing Cardiovascular Collection focussed on blood pressure, coronary heart disease and heart failure. In this second collection, publications since 2011 were selected with emphasis on atrial fibrillation, transient ischaemic attack (TIA) and stroke. The prevalence of TIA and stroke increases as people get older. In this commentary we summarise studies published in Age and Ageing that bring to the fore the need for a multidisciplinary, person-centred approach to care, conscientious identification of risk factors and their management and prevention strategies, which will inform policy ultimately reducing the burden of cost placed by stroke care on healthcare financing. Read the latest Cardiovascular Collection here.

Systematic review of the relationship between Hollenhorst plaques and cerebrovascular events.

BACKGROUND: Few studies have evaluated the association between asymptomatic cholesterol emboli on fundoscopy (known as Hollenhorst plaque) and the subsequent risk of stroke or death.1. AIM: To evaluate the association between the presence of asymptomatic cholesterol retinal emboli and the risk of cerebrovascular events, with assessment of the need for carotid intervention. METHODS: PubMed, Embase, and Cochrane Library databases were searched using appropriate terms. The systematic review was conducted according to PRISMA guidelines. RESULTS: Initial search revealed 43 in Medline and 46 in Embase databases. Twenty-four potentially eligible studies were included after duplicate and non-related studies were excluded based on title and abstract. Three more studies were identified from reference lists. Seventeen studies were included in the final analysis. Asymptomatic cholesterol emboli were present in 1343 patients. Approximately 17.8% (n = 181) had history of either cerebro-vascular Accident (CVA) or transient ischaemic attacks (TIAs) at presentation (more than 6 months). Nine studies mentioned the incidence of cerebrovascular events during follow-up. Of 780 patients, 93 evolved to stroke, TIAs, or death from a major carotid event during the follow-up period (6-86 m), an incidence of about 12%. Death due to stroke was documented in 3 studies (n = 12). CONCLUSION: The presence of asymptomatic retinal emboli indicates a risk of a cerebrovascular event when compared to patients with no plaques seen on fundoscopy. The evidence suggests that these patients warrant referral for medical optimization of cardiovascular risk factors. Currently, there is no recommendation to support carotid endarterectomy in patients with Hollenhorst plaques, or retinal emboli, and further studies are needed to assess this.

Using measures of sarcopenia to predict recurrent cerebrovascular events in stroke and TIA patients.

PURPOSE: Sarcopenia is associated with poor outcomes, and evidence suggests an inverse relationship between skeletal muscle mass and cardiovascular risk. Sarcopenia has been studied after stroke, but its value as a risk factor for stroke has not been examined. This prospective cohort study measured sarcopenia in stroke/TIA patients at baseline to explore its role in predicting recurrent events. METHOD: The Arterial Stiffness In lacunar Stroke and TIA (ASIST) study included 96 patients with TIA/lacunar stroke, of which 82 patients (mean age 71.2±10.8 years) had bioimpedance analysis to assess body composition. Skeletal Mass Index (SMI) was calculated and parameters of sarcopenia assessed using Davison (1) and Janssen (2) criteria. Recurrent cerebrovascular events were monitored over 5 years. RESULTS: Eighteen patients had recurrent events. On independent samples t test there were significantly more participants with sarcopenia in the recurrent events group (89% vs 56%, p<0.001) using Davison (1) criteria, as well as lower mean SMI, significantly more participants with diabetes and higher arterial stiffness. On binary logistic regression, the only significant predictors of recurrent events were SMI (p=0.036, hazard ratio=0.414, 95% confidence interval 0.195-0.948) and diabetes (p=0.004, hazard ratio=9.06, 95% confidence interval 2.009-40.860) when corrected for age, sex and cardiovascular risk factors. Using Janssen (2) criteria in the regression, severe sarcopenia was a significant predictor of recurrent events (p=0.028). There was a significant association between sarcopenia and recurrent events on Chi square based on Davison (p=0.02) and Janssen (p=0.034) definitions. CONCLUSIONS: The presence of baseline sarcopenia in stroke and TIA patients is an independent predictor of recurrent events.

Stroke and emergency department re-presentation after outpatient TIA management: An interrupted time series study.

OBJECTIVES: To assess the effects of a non-admitted management pathway following emergency department (ED) presentation with suspected TIA on: 90-day stroke and ED re-presentations, overnight admission, length of stay (LOS) and costs. METHODS: We implemented a management pathway across an Australian regional health service (4 hospitals; 2 rural, 10,000 km2) including ED protocols followed by urgent outpatient review or telemedicine consultation to one rural hospital. Interrupted time series analysis was conducted on linked hospital administrative datasets for all ED TIA diagnoses 5 years before and 2 years after intervention (2015). We assessed whether pathway introduction was associated with immediate change (level) or subsequent rate of change (slope) in outcomes. RESULTS: There were 2031 presentations: 1,467 before, 564 after implementation. Against background declining trends, overnight admissions decreased by 12.4% (95%CI 5.0, 19.7) and total LOS decreased 6 hours (95%CI 1.5, 10.4). Hospital costs reduced by AUD683 per patient with implementation. Outpatient review occurred for 36% at median 5 days (IQR 3, 9), including 19/87 (22%) telemedicine reviews. Pathway adherence was incomplete: 29% had no specialist review. Recurrent stroke increased by 1.3/100 presentations (95%CI 0.6, 2.1) with implementation, then returned to baseline of 0.9/100. ED re-presentations rose at a significant rate after implementation (extra 1.69/100 patients re-presenting/quarter; 95%CI 0.8, 2.6) reaching 32/100. CONCLUSIONS: An ED TIA management pathway designed to avoid hospital admission resulted in decreased hospital use and costs; but an initial increase in recurrent stroke and sustained rise in ED re-presentation, possibly related to delayed and incomplete follow-up.

Machine learning-based identification of symptomatic carotid atherosclerotic plaques with dual-energy computed tomography angiography.

OBJECTIVE: This study aimed to develop and validate a machine learning model incorporating both dual-energy computed tomography (DECT) angiography quantitative parameters and clinically relevant risk factors for the identification of symptomatic carotid plaques to prevent acute cerebrovascular events. METHODS: The data of 180 patients with carotid atherosclerosis plaques were analysed from January 2017 to December 2021; 110 patients (64.03±9.58 years old, 20 women, 90 men) were allocated to the symptomatic group, and 70 patients (64.70±9.89 years old, 50 women, 20 men) were allocated to the asymptomatic group. Overall, five machine learning models using the XGBoost algorithm, based on different CT and clinical features, were developed in the training cohort. The performances of all five models were assessed in the testing cohort using receiver operating characteristic curves, accuracy, recall rate, and F1 score. RESULTS: The shapley additive explanation (SHAP) value ranking showed fat fraction (FF) as the highest among all CT and clinical features and normalised iodine density (NID) as the 10th. The model based on the top 10 features from the SHAP measurement showed optimal performance (area under the curve [AUC] .885, accuracy .833, recall rate .933, F1 score .861), compared with the other four models based on conventional CT features (AUC .588, accuracy .593, recall rate .767, F1 score .676), DECT features (AUC .685, accuracy .648, recall rate .667, F1 score .678), conventional CT and DECT features (AUC .819, accuracy .740, recall rate .867, F1 score .788), and all CT and clinical features (AUC .878, accuracy .833, recall rate .867, F1 score .852). CONCLUSION: FF and NID can serve as useful imaging markers of symptomatic carotid plaques. This tree-based machine learning model incorporating both DECT and clinical features could potentially comprise a non-invasive method for identification of symptomatic carotid plaques to guide clinical treatment strategies.

Low-Density Lipoprotein Cholesterol Treatment Target Achievement in Patients with Myocardial Infarction, Percutaneous Coronary Intervention, or Stroke in Hong Kong.

Background: Elevated concentrations of low-density lipoprotein cholesterol (LDL-C) are an important cause of recurrent cardiovascular events. This study aimed to describe the distribution and achieved concentrations of LDL-C among patients with myocardial infarction (MI), percutaneous coronary intervention (PCI), stroke, or transient ischaemic attack (TIA) in Hong Kong. Methods: Patients with a lipid test from a public hospital were identified from the Clinical Database and Analysis Reporting System of the Hong Kong Hospital Authority. Among patients with an inpatient hospitalization for MI, PCI, stroke or TIA, between 2003 to 2016, the distribution of LDL-C levels and the number (%) of patients achieving an absolute concentration of LDL-C < 1.8 mmol/L at baseline (in-hospital) and during 12 months after hospital discharge were described. Results: A total of 18417 patients were included (mean [SD] age, 70.0 [12.9] years; male, 60.3%), of which 3637 had MI, 4096 had PCI, and 10684 had stroke or TIA. At hospital discharge 12082 (65.6%) patients were prescribed statins, 690 (3.7%) were prescribed nonstatins, and 1849 (10.0%) achieved an LDL-C < 1.8 mmol/L. Overall, 5654 (30.7%) patients did not have LDL-C result available within 12 months of discharge (MI, 605 [16.6%]; PCI, 432 [10.5%]; stroke or TIA, 4617 [43.2%]). Among the overall cohort, 4591 (24.9%) patients achieved an LDL-C < 1.8 mmol/L during 12 months of follow-up (MI, 1288 [35.4%]; PCI, 1542 [37.6%]; stroke or TIA, 1761 [16.5%]). Improvements in achieved LDL-C were observed over time with a mean LDL-C 2.64 (0.92) mmol/L and 20.0% of patients achieving an LDL-C < 1.8 mmol/L in 2003 as compared with a mean LDL-C 1.86 (0.70) mmol/L and 53.9% of patients achieving an LDL-C < 1.8 mmol/L in 2016. Conclusions: In this single centre cohort study from Hong Kong, nearly half of patients with MI, PCI, or stroke in 2016 appear to qualify for intensification of lipid-modifying drug treatment in order to achieve a treatment goal of LDL-C < 1.8 mmol/L. Further research is required in Hong Kong to assess contemporary management of LDL-C in a larger group of patients with established atherosclerotic cardiovascular disease.

Management of pulmonary arteriovenous malformations involves additional factors aside from the diameter of feeding arteries: a 3-year case-case retrospective analysis.

BACKGROUND: Pulmonary arteriovenous malformations (PAVMs) are rare but cause various manifestations. Although the diameter of feeding arteries has been linked to treatment decisions, relationships among the characteristics of PAVMs, clinical symptoms, and treatment effect remain unclear. The present study was performed to investigate how collective characteristics of PAVMs relate to clinical symptoms and to provide proper treatment recommendations for patients with PAVMs. METHODS: We retrospectively analysed 838,447 patients' radiographic data and medical records from January 2018 to December 2020. Patients were included if a PAVM was radiographically detected for the first time in our hospital. Ordered multivariable logistic regression and hierarchical multiple regression were performed to analyse the relationships between characteristics of PAVMs and various clinical symptoms. We investigated the management of PAVMs in four tertiary university hospitals. RESULTS: Detection rate of PAVMs was 0.025% (207/838,447), and 37.6% of patients (78/207) also had hereditary haemorrhagic telangiectasia. Eight patients were diagnosed with bilateral diffuse PAVMs. Two hundred thirty-six lesions were detected in 199 patients, and the mean diameter of the feeding artery was 4.13 ± 1.92 mm. Most PAVMs were the simple type and located in the peripheral pulmonary area. In total, 34.3% of patients (71/207) were symptom-free; remaining patients showed various manifestations, and respiratory symptoms were most common (dyspnoea on exertion, 47.8%). The diameter of the feeding artery and the type and the number of PAVMs were correlated with hypoxaemia (P < 0.001, P < 0.001, and P = 0.037, respectively). The collective characteristics of PAVMs were not related to the severity of central nervous system symptoms (largest diameter of feeding artery, P = 0.8; largest diameter of sac, P = 0.42; number of PAVMs, P = 0.35; type of PAVMs, P = 0.99). Various symptoms were greatly relieved after treatment. The hospital investigation showed that management of PAVMs was not generally appreciated in clinical practice. CONCLUSIONS: Our study revealed a low detection rate of PAVMs and a low degree of association with hereditary haemorrhagic telangiectasia in the general population. Considering the connection between collective characteristics of PAVMs and various clinical symptoms, clinicians should consider the type and number of PAVMs, the largest diameter of the feeding artery, and clinical symptoms when managing patients with PAVMs.

Does prior use of antiplatelet therapy modify the effect of dual antiplatelet therapy in transient ischaemic attack/minor ischaemic stroke: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: The purpose was to determine whether prior use of antiplatelet therapy modifies the effect of dual antiplatelet therapy in patients with acute minor ischaemic stroke or transient ischaemic attack. METHODS: A systematic review and meta-analysis of randomized controlled trials was performed comparing dual antiplatelet therapy to aspirin that reported subgroup analysis by prior antiplatelet use, adhering to the Cochrane Collaboration Guidelines. A fixed-effects meta-analysis was used to estimate a pooled treatment effect overall in subgroups with prior aspirin therapy and without prior aspirin therapy. Difference in treatment effect was assessed by testing p for interaction. The primary outcome measure was recurrent vascular events. RESULTS: Three eligible randomized controlled trials were identified, including 4831 participants with pre-existing antiplatelet use and 16,236 participants without pre-existing aspirin use. Recurrent vascular events occurred in 7.2% (95% confidence interval [CI] 4.3-10) of those without pre-existing aspirin use versus 7.3% (95% CI 4.1-10) of those receiving prior aspirin therapy. Effect of dual antiplatelet therapy on the primary outcome measure was consistent in participants with no prior aspirin use (odds ratio 0.75, 95% CI 0.66-0.84) compared to those taking aspirin before randomization (odds ratio 0.79, 95% CI 0.63-0.998) (p interaction = 0.66). The number needed to treat in the aspirin-naïve group was 55 (95% CI 37-107) compared to 66 (95% CI 32 to -746) in those on prior aspirin therapy. CONCLUSIONS: It was found that the effectiveness of dual antiplatelet therapy in patients with minor ischaemic stroke or high risk transient ischaemic attack does not significantly differ in patients with prior aspirin exposure; therefore there should be no influence on the decision to use dual antiplatelet therapy.

Increased frequency of CYP2C19 loss-of-function alleles in clopidogrel-treated patients with recurrent cerebral ischemia.

AIMS: Clopidogrel is used as secondary prevention after cerebral ischaemia. Previous, mainly Asian, studies have shown that genetic variations in CYP2C19 are associated with an increased risk of recurrent stroke in clopidogrel-treated patients. Evidence on the impact of this drug-gene interaction in European neurology patients is currently limited. The aim of this study is to compare the prevalence of CYP2C19 loss-of-function (LoF) alleles in a population with recurrent cerebral ischaemia to two reference groups from the same region. METHODS: CYP2C19-genotyping (*2 and *3) was performed in clopidogrel-treated patients who presented with a recurrent ischaemic stroke/transient ischaemic attack (TIA). Genotype distributions were compared with two reference groups; a cohort of consecutive patients who underwent elective coronary stent implantation and a cohort of healthy Dutch volunteers. RESULTS: In total, 188 cases with a recurrent ischaemic event were identified, of whom 38 (20.2%) experienced an early recurrent event (24 hours to 90 days after the previous event). Among the total case group, 43.6% of the patients carried at least one CYP2C19 LoF allele, compared with 27.6% and 24.7% in respectively the cardiology and the healthy volunteers reference groups (P < .001 for both comparisons). Among the cases with an early recurrent event, 55.3% of patients were carriers of at least one CYP2C19 LoF allele (P < .0001). CONCLUSION: In this clopidogrel-treated population with recurrent cerebral ischaemia, the frequency of CYP2C19 LoF alleles was significantly higher than in reference groups, especially in early recurrent events. This study adds to the growing body of evidence that genotype-guided antiplatelet therapy could improve patient outcomes.

Dose-Dependent Association of Inflammatory Cytokines with Carotid Atherosclerosis in Transient Ischaemic Attack: Implications for Clinical Trials.

INTRODUCTION: The 5-year recurrence risk after ischaemic stroke and transient ischaemic attack (TIA) is 25-30%. Although inflammation may be a target for prevention trials, the contribution of plaque inflammation to acute cerebrovascular events remains unclear. We investigated the association of acute inflammatory cytokines and high-sensitivity C-reactive protein (CRP) with recently symptomatic carotid atherosclerosis in a prospective cohort study. METHODS: Blood and Imaging markers of TIA BIO-TIA) is a multicentre prospective study of imaging and inflammatory markers in patients with TIA. Exclusion criteria were infection and other co-morbid illnesses associated with inflammation. CRP and serum cytokines (interleukin [IL]-6, IL-1ß, IL-8, IL-10, IL-12, interferon-γ [IFN-γ] and tumour necrosis factor-α [TNF-α]) were measured. All patients had carotid imaging. RESULTS: Two hundred and thirty-eight TIA cases and 64 controls (TIA mimics) were included. Forty-nine (20.6%) cases had symptomatic internal carotid artery stenosis. Pro-inflammatory cytokine levels increased in a dose-dependent manner across controls, TIA without carotid stenosis (CS), and TIA with CS (IL-1ß, ptrend = 0.03; IL-6, ptrend < 0.0001; IL-8, ptrend = 0.01; interferon (IFN)-γ, ptrend = 0.005; TNF-α, ptrend = 0.003). Results were unchanged when DWI-positive cases were excluded. On multivariable linear regression, only age (p = 0.01) and CS (p = 0.04) independently predicted log-IL-6. On multivariable Cox regression, CRP was the only independent predictor of 90-day stroke recurrence (adjusted hazard ratio per 1-unit increase 1.03 [95% CI: 1.01-1.05], p = 0.003). CONCLUSION: Symptomatic carotid atherosclerosis was associated with elevated cytokines in TIA patients after controlling for other sources of inflammation. High-sensitivity CRP was associated with recurrent ischaemic stroke at 90 days. These findings implicate acute plaque inflammation in the pathogenesis of cerebral thromboembolism and support a rationale for randomized trials of anti-inflammatory therapy for stroke patients, who were excluded from coronary trials.

Cerebrovascular Disease Profiles of Culturally and Linguistically Diverse Communities in South Western Sydney and New South Wales.

INTRODUCTION: Culturally and linguistically diverse (CALD) communities are growing globally. Understanding patterns of cerebrovascular disease in CALD communities may improve health outcomes through culturally specific interventions. We compared rates of transient ischaemic attack (TIA)/stroke (ischaemic stroke, intracerebral haemorrhage) and stroke risk factor prevalence in overseas and Australian-born people in South Western Sydney (SWS) and New South Wales (NSW). METHODS: This was a 10-year retrospective analysis (2011-2020) of SWS and NSW age-standardized rates per 100,000 person-years of TIA/stroke. Data were extracted from Health Information Exchange and Secure Analytics for Population Health Research and Intelligence systems. Rates of hypertension, type 2 diabetes mellitus (T2DM), atrial fibrillation (AF), smoking, and obesity were also calculated. RESULTS: The SWS and NSW age-standardized rate of TIA/stroke for people born in Australia was 100 per 100,000 person-years (100/100,000/year). In SWS, 56.6% of people were overseas-born compared to 29.8% for NSW. The age-standardized rate of TIA/stroke for Polynesian-born people was more than double that of Australian-born people (p < 0.001). Hypertension (33 [SWS] vs. 27/100,000/year [NSW]) and T2DM (36 [SWS] vs. 26/100,000/year [NSW]) were the most common risk factors with rates >50/100,000/year (hypertension) and >80/100,000/year (T2DM) for people born in Polynesia, Melanesia, and Central America. Rates of T2DM, AF, and obesity for Polynesian-born people were over threefold greater than people born in Australia. DISCUSSION/CONCLUSION: Greater rates of TIA/stroke were observed in specific CALD communities, with increased rates of cerebrovascular risk factors. Culturally specific, targeted interventions may bridge health inequalities in cerebrovascular disease.

Long-term outcome of a pragmatic trial of multifaceted intervention (STROKE-CARD care) to reduce cardiovascular risk and improve quality-of-life after ischaemic stroke and transient ischaemic attack: study protocol.

BACKGROUND: Patients with ischaemic stroke or transient ischaemic attack (TIA) are at high risk of incident cardiovascular events and recurrent stroke. Despite compelling evidence about the efficacy of secondary prevention, a substantial gap exists between risk factor management in real life and that recommended by international guidelines. We conducted the STROKE-CARD trial (NCT02156778), a multifaceted pragmatic disease management program between 2014 and 2018 with follow-up until 2019. This program successfully reduced cardiovascular risk and improved health-related quality of life and functional outcome in patients with acute ischaemic stroke or TIA within 12 months after the index event. To investigate potential long-term effects of STROKE-CARD care compared to standard care, an extension of follow-up is warranted. METHODS: We aim to include all patients from the STROKE-CARD trial (n = 2149) for long-term follow-up between 2019 and 2021 with the study visit scheduled 3-6 years after the stroke/TIA event. The co-primary endpoint is the composite of major recurrent cardiovascular events (nonfatal stroke, nonfatal myocardial infarction, and vascular death) from hospital discharge until the long-term follow-up visit and health-related quality of life measured with the European Quality of Life-5 Dimensions (EQ-5D-3L) at the final visit. Secondary endpoints include overall mortality, long-term functional outcome, and target-level achievement in risk factor management. DISCUSSION: This long-term follow-up will provide evidence on whether the pragmatic post-stroke/TIA intervention program STROKE-CARD is capable of preventing recurrent cardiovascular events and improving quality-of-life in the long run. Trial registration clinicaltrials.gov: NCT04205006 on 19 December 2019.

Does infection predispose to thrombosis during long-term ventricular assist device support?

BACKGROUND: Infections and thrombotic events remain life-threatening complications in patients with ventricular assist devices (VAD). METHODS: We describe the relationship between both events in our cohort of patients (n = 220) supported with the HeartWare VAD (HVAD). This is a retrospective analysis of patients undergoing HVAD implantation between July 2009 and March 2019 at the Freeman Hospital, Newcastle upon Tyne, United Kingdom. RESULTS: Infection was the most common adverse event in HVAD patients, with 125 patients (56.8%) experiencing ≥ one infection (n = 168, 0.33 event per person year (EPPY)), followed by pump thrombosis (PT) in 61 patients (27.7%, 0.16 EPPY). VAD-specific infections were the largest group of infections. Of the 125 patients who had an infection, 66 (53%) had a thrombotic event. Both thrombotic events and infections were related to the duration of support, though there was only limited evidence that infections predispose to thrombosis. Those with higher than median levels of C-reactive protein during the infection were more likely to have an ischaemic stroke (IS) (34.5% vs 16.7%, p = .03), though not PT or a combined thrombotic event (CTE: first PT or IS). However, in multivariate analysis, there was no significant effect of infection predisposing to CTE. CONCLUSIONS: Infection and thrombotic events are significant adverse events related to the duration of support in patients receiving HVADs. Infections do not clearly predispose to thrombotic events.