Randomization of endovascular treatment with stent-retriever and/or thromboaspiration versus best medical therapy in acute ischemic stroke due to large vessel occlusion trial: Rationale and design.

BACKGROUND: RESILIENT is a prospective, multicenter, randomized phase III trial to test the safety, efficacy, and cost-effectiveness of mechanical thrombectomy as compared to medical treatment alone in patients treated under the less than ideal conditions typically found in the public healthcare system of a developing country. METHODS: Subjects must fulfill the following main inclusion criteria: symptom onset ≤8 h, age ≥18 years, baseline NIHSS ≥8, evidence of intracranial ICA or proximal MCA (M1 segment) occlusion, ASPECTS ≥6 on CT or >5 on DWI-MRI and be either ineligible for or unresponsive to intravenous alteplase. The primary end-point is the distribution of disability levels (on the modified Rankin Scale, mRS) at 90 days under the intention-to-treat principle. RANDOMIZATION: Randomization is performed under a minimization process using age, baseline NIHSS, intravenous alteplase use, occlusion site and center. DESIGN: The trial is designed with an expectation of a 10% difference in the proportion of favorable outcome (mRS 0-2 at 90 days) common odds ratio of 1.615. PRIMARY OUTCOME: Projected sample size is 690 subjects with pre-planned interim analyses at 174, 346, and 518 subjects. SECONDARY OUTCOMES: Secondary end-points include: 90-day functional independence (mRS ≤2), mRS shift stratified for treatment with IV rt-PA at 90 days, infarct volume on 24 h CT or MRI, early dramatic response (NIHSS 0-2 or improvement ≥8 points) at 24 h, vessel recanalization evaluated by CTA or MRA at 24 h, and the post-procedure rate of successful reperfusion (defined as a modified Treatment in Cerebral Infarction 2b or greater). Safety variables are mortality at 90 days, symptomatic intracranial hemorrhage at 24 h and procedure-related complications.

Thrombectomy for Stroke in the Public Health Care System of Brazil.

BACKGROUND: Randomized trials involving patients with stroke have established that outcomes are improved with the use of thrombectomy for large-vessel occlusion. These trials were performed in high-resource countries and have had limited effects on medical practice in low- and middle-income countries. METHODS: We studied the safety and efficacy of thrombectomy in the public health system of Brazil. In 12 public hospitals, patients with a proximal intracranial occlusion in the anterior circulation that could be treated within 8 hours after the onset of stroke symptoms were randomly assigned in a 1:1 ratio to receive standard care plus mechanical thrombectomy (thrombectomy group) or standard care alone (control group). The primary outcome was the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. RESULTS: A total of 300 patients were enrolled, including 79 who had undergone thrombectomy during an open-label roll-in period. Approximately 70% in the two groups received intravenous alteplase. The trial was stopped early because of efficacy when 221 of a planned 690 patients had undergone randomization (111 to the thrombectomy group and 110 to the control group). The common odds ratio for a better distribution of scores on the modified Rankin scale at 90 days was 2.28 (95% confidence interval [CI], 1.41 to 3.69; P = 0.001), favoring thrombectomy. The percentage of patients with a score on the modified Rankin scale of 0 to 2, signifying an absence of or minor neurologic deficit, was 35.1% in the thrombectomy group and 20.0% in the control group (difference, 15.1 percentage points; 95% CI, 2.6 to 27.6). Asymptomatic intracranial hemorrhage occurred in 51.4% of the patients in the thrombectomy group and 24.5% of those in the control group; symptomatic intracranial hemorrhage occurred in 4.5% of the patients in each group. CONCLUSIONS: In this randomized trial conducted in the public health care system of Brazil, endovascular treatment within 8 hours after the onset of stroke symptoms in conjunction with standard care resulted in better functional outcomes at 90 days than standard care alone. (Funded by the Brazilian Ministry of Health; RESILIENT ClinicalTrials.gov number, NCT02216643.).

Impact of simulation training on a telestroke network.

BACKGROUND: Stroke is a leading cause of morbidity and mortality in Brazil, where there are significant imbalances in access to specialized stroke care. Telemedicine networks allow patients to receive neurological evaluation and intravenous thrombolysis in underserved areas, where performance measures are challenging. AIMS: To describe the impact caused by adequate stroke care training, using realistic simulation, in a developing country telestroke network. METHODS: Retrospective observational study comparing the number of all stroke diagnoses, thrombolysis rate, door-to-needle time and symptomatic intracranial hemorrhage after intravenous thrombolysis, during one year providing just algorithms and orientation in stroke care to spoke facilities (phase 1), with the results achieved along one year after the beginning of ongoing live training sessions (phase 2). RESULTS: The mean number of patients diagnosed with stroke increased from 7.5 to 16.58 per month (P = 0.019) rising from 90 patients during phase 1 to 199 in phase 2. There was a reduction in the mean door-to-needle time from 137.1 to 95.5 min (-41.58; 95% CI -62.77 to -20.40). The thrombolysis and symptomatic intracranial hemorrhage rates had a non-significant decrease from 21.31% to 18.18% (OR 0.82; 95% CI 0.39 to 1.71) and 12.5% to 7.69% (OR 0.58; 95% CI 0.046 to 7.425), respectively. CONCLUSIONS: Realistic simulation stroke care training provided by stroke centers to spoke facilities seems to significantly reduce door-to-needle time and enhance adherence in a telestroke network.

Brazilian guidelines for endovascular treatment of patients with acute ischemic stroke.

These guidelines are the result of a joint effort from writing groups of the Brazilian Stroke Society, the Scientific Department of Cerebrovascular Diseases of the Brazilian Academy of Neurology, the Brazilian Stroke Network and the Brazilian Society of Diagnostic and Therapeutic Neuroradiology. Members from these groups participated in web-based discussion forums with predefined themes, followed by videoconference meetings in which controversies and position statements were discussed, leading to a consensus. This guidelines focuses on the implications of the recent clinical trials on endovascular therapy for acute ischemic stroke due to proximal arterial occlusions, and the final text aims to guide health care providers, health care managers and public health authorities in managing patients with this condition in Brazil.

Brazilian guidelines for endovascular treatment of patients with acute ischemic stroke / Diretrizes brasileiras para o tratamento endovascular de pacientes com acidente vascular cerebral isquêmico agudo

ABSTRACT These guidelines are the result of a joint effort from writing groups of the Brazilian Stroke Society, the Scientific Department of Cerebrovascular Diseases of the Brazilian Academy of Neurology, the Brazilian Stroke Network and the Brazilian Society of Diagnostic and Therapeutic Neuroradiology. Members from these groups participated in web-based discussion forums with predefined themes, followed by videoconference meetings in which controversies and position statements were discussed, leading to a consensus. This guidelines focuses on the implications of the recent clinical trials on endovascular therapy for acute ischemic stroke due to proximal arterial occlusions, and the final text aims to guide health care providers, health care managers and public health authorities in managing patients with this condition in Brazil.

RESUMO Estas diretrizes são o resultado de um esforço conjunto de membros da Sociedade Brasileira de Doenças Cerebrovasculares (SBDCV), Departamento científico de Doenças Cerebrovasculares da Academia Brasileira de Neurologia (ABN), Rede Brasil AVC (RBAVC) e da Sociedade Brasileira de Neurorradiologia Diagnóstica e Terapêutica (SBNR). Membros destas 4 entidades participaram de fórum de discussões por internet de temas pré-definidos, seguidos de encontros de videoconferência para discussão de pontos controversos e das recomendações, em busca de um consenso final. Estas diretrizes tem seu foco sobre as implicações dos recentes ensaios clínicos de tratamento endovascular do acidente vascular cerebral (AVC) isquêmico agudo relacionado a oclusão de artérias proximais. O texto final foi elaborado para servir de orientação no manejo destes pacientes AVC isquêmico pelos diferentes profissionais de saúde, gestores de saúde pública e de saúde complementar no Brasil.

Obesity, Insulin Resistance, and Incident Small Vessel Disease on Magnetic Resonance Imaging: Atherosclerosis Risk in Communities Study.

BACKGROUND AND PURPOSE: The term metabolic syndrome describes the clustering of risk factors found in many individuals with obesity. Because of their pathophysiology, we hypothesized that 2 features of metabolic syndrome, central obesity and insulin resistance (IR), would be associated with cerebrovascular changes on magnetic resonance imaging, and specifically with incident lacunar disease and not white matter hyperintensity (WMH) progression. METHODS: Risk factors were defined at study baseline in 934 participants in the Atherosclerosis Risk in Communities (ARIC) study, who completed 2 brain magnetic resonance imagings≈10 years apart. WMH progression and incident lacunes between the 2 magnetic resonance imagings were determined. An IR score for each participant was created using principal component analysis of 11 risk factors, including (among others): insulin, homeostatic model assessment-IR, body mass index, and waist circumference. Metabolic syndrome (presence/absence), using standard clinical definitions, and IR score at the first magnetic resonance imaging, were independent variables, evaluated in multivariate logistic regression to determine odds of WMH progression (Q5 versus Q1-Q4) and incident lacunes. RESULTS: Metabolic syndrome (adjusted odds ratio, 1.98; 95% confidence interval, 1.28-3.05) and IR score (adjusted odds ratio per 1-SD increase, 1.33; 95% confidence interval, 1.05-1.68) were associated with incident lacunes but not with WMH progression. Insulin, homeostatic model assessment-IR, and body mass index were not associated with incident lacunes or WMH progression in separate models. CONCLUSIONS: The IR score and central obesity are associated with incident lacunar disease but not WMH progression in individuals. Central obesity and IR may be important risk factors to target to prevent lacunar disease.

Small Brain Lesions and Incident Stroke and Mortality: A Cohort Study.

BACKGROUND: Although cerebral lesions 3 mm or larger on imaging are associated with incident stroke, lesions smaller than 3 mm are typically ignored. OBJECTIVE: To examine stroke risks associated with subclinical brain lesions (<3 mm only, ≥3 mm only, and both sizes) and white matter hyperintensities (WMHs). DESIGN: Community cohort from the ARIC (Atherosclerosis Risk in Communities) Study. SETTING: Two ARIC sites with magnetic resonance imaging (MRI) data from 1993 to 1995. PARTICIPANTS: 1884 adults aged 50 to 73 years with MRI, no prior stroke, and average follow-up of 14.5 years. MEASUREMENTS: Lesions on MRI (by size), WMH score (scale of 0 to 9), incident stroke, all-cause mortality, and stroke-related mortality. Hazard ratios (HRs) were estimated with proportional hazards models. RESULTS: Compared with no lesions, stroke risk tripled with lesions smaller than 3 mm only (HR, 3.47 [95% CI, 1.86 to 6.49]), doubled with lesions 3 mm or larger only (HR, 1.94 [CI, 1.22 to 3.07]), was 8-fold higher with lesions of both sizes (HR, 8.59 [CI, 4.69 to 15.73]), and doubled with a WMH score of at least 3 (HR, 2.14 [CI, 1.45 to 3.16]). Risk for stroke-related death tripled with lesions smaller than 3 mm only (HR, 3.05 [CI, 1.04 to 8.94]) and was 7 times higher with lesions of both sizes (HR, 6.97 [CI, 2.03 to 23.93]). LIMITATION: Few strokes (especially hemorrhagic) and few participants with lesions smaller than 3 mm only or lesions of both sizes. CONCLUSION: Very small cerebrovascular lesions may be associated with increased risks for stroke and death; presence of lesions smaller than 3 mm and 3 mm or larger may result in a particularly striking risk increase. Larger studies are needed to confirm findings and provide more precise estimates. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

Carotid intima-media thickness value distributions in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

OBJECTIVE: Carotid intima-media thickness (IMT) is a noninvasive measurement of early atherosclerosis. Most IMT studies have involved populations with low rates of racial blending. The aim of the present article is to describe IMT value distributions and analyze the influence of sex and race on IMT values in a large Brazilian sample, a setting with a high rate of racial admixture. METHODS: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) is a multicenter cohort of 15,105 adult (aged 35-74 years) civil servants in six Brazilian cities. Baseline assessment included IMT measurements in both common carotid arteries. Race was self-reported. We studied the association between sex and race with IMT values using multiple linear regression models. We conducted analyses in all and low-risk individuals, defined as those without classical cardiovascular risk factors. RESULTS: We analyzed complete IMT data from 10,405 ELSA-Brasil participants. We present nomograms by age for all and low-risk individuals, stratified by sex and race. We found that men had significantly higher maximal IMT values compared with women (ß = 0.058; P < 0.001). This association remained for low-risk individuals (ß = 0.027; P = 0.001). In addition, Brown and White individuals had lower maximal IMT values compared with Black individuals for all (ß = -0.034 and ß = -0.054, respectively; P < 0.001) and low-risk individuals (ß = -0.027; P = 0.013 and ß = -0.035; P < 0.001, respectively). CONCLUSION: We found significantly higher IMT values in men. We found significantly higher IMT values in Black individuals than White and Brown individuals. These results persisted when analyses were restricted to low-risk individuals.

CT angiography helps to differentiate acute from chronic carotid occlusion: the "carotid ring sign".

INTRODUCTION: Currently, there is no reliable method to differentiate acute from chronic carotid occlusion. We propose a novel CTA-based method to differentiate acute from chronic carotid occlusions that could potentially aid clinical management of patients. METHODS: We examined 72 patients with 89 spontaneously occluded extracranial internal carotids with CT angiography (CTA). All occlusions were confirmed by another imaging modality and classified as acute (imaging <1 week of presumed occlusion) orchronic (imaging >4 weeks), based on circumstantial clinical and radiological evidence. A neuroradiologist and a neurologist blinded to clinical information determined the site of occlusion on axial sections of CTA. They also looked for (a) hypodensity in the carotid artery (thrombus), (b) contrast within the carotid wall (vasa vasorum), (c) the site of the occluded carotid, and (d) the "carotid ring sign" (defined as presence of a and/or b). RESULTS: Of 89 occluded carotids, 24 were excluded because of insufficient circumstantial evidence to determine timing of occlusion, 4 because of insufficient image quality, and 3 because of subacute timing of occlusion. Among the remaining 45 acute and 13 chronic occlusions, inter-rater agreement (kappa) for the site of proximal occlusion was 0.88, 0.45 for distal occlusion, 0.78 for luminal hypodensity, 0.82 for wall contrast, and 0.90 for carotid ring sign. The carotid ring sign had 88.9% sensitivity, 69.2% specificity, and 84.5% accuracy to diagnose acute occlusion. CONCLUSION: The carotid ring sign helps to differentiate acute from chronic carotid occlusion. If further confirmed, this information may be helpful in studying ischemic symptoms and selecting treatment strategies in patients with carotid occlusions.

Prognostic value of exercise-induced ventricular arrhythmia in Chagas' heart disease.

OBJECTIVE: To determine the prevalence and the prognostic value of exercise-induced ventricular arrhythmia (EIVA) in chronic Chagas' heart disease. STUDY DESIGN AND SETTING: An open prospective cohort of 130 clinically stable patients at a University Hospital outpatient unit in Rio de Janeiro, Brazil, was followed up at scheduled clinical visits from 1990 through 2007. The endpoint was total cardiovascular mortality. Survival curves (Kaplan-Meier) and a multivariate Cox proportional hazard model were adjusted to determine the association between EIVA and mortality. RESULTS: The median duration of follow-up was 9.9 years (range, 132 days to 17 years). EIVA prevalence was 43.1% (95% CI: 34.5-51.7). Thirty-three cardiovascular deaths (25.4%) occurred. The hazard ratio of EIVA for cardiovascular death, after adjustment for age, was 1.84 (P = 0.09). An interaction was found between EIVA and cardiomegaly on x-ray. In the group with cardiomegaly, the hazard of dying was four times greater in the presence of EIVA (P for interaction = 0.05). CONCLUSION: In clinically stable chagasic subjects with cardiomegaly, EIVA is a clinically significant marker of total cardiovascular mortality and may be a useful risk stratification tool in this population.

Antiplatelets in stroke prevention: the MATCH trial. Some answers, many questions and countless perspectives.

Antiplatelet drugs have an established efficacy in the secondary prevention of ischemic stroke. The recent results of the CAPRIE, CURE, and CREDO studies formed the rationale for the MATCH, designed to test whether the association of clopidogrel and aspirin was better than clopidogrel alone for the prevention of vascular events among high-risk ischemic cerebrovascular patients. Although the benefits were outweighed for a higher bleeding risk in the combination group, this study will provide important insight for upcoming trials in other to determine what populations might mostly benefit from these drugs for the secondary prevention of stroke in the future.

Effect of discontinuing aspirin therapy on the risk of brain ischemic stroke.

BACKGROUND: Aspirin, or acetylsalicylic acid, is widely used to prevent ischemic vascular disease. Clinical and experimental data suggest that a rebound effect occurs 4 or fewer weeks after interruption of aspirin therapy. OBJECTIVE: To study the discontinuation of aspirin therapy as a risk factor for ischemic stroke (IS). DESIGN: Case-control study. SETTING: Stroke unit. PARTICIPANTS: Three hundred nine patients with IS or transient ischemic attack undergoing long-term aspirin treatment before their index event and 309 age-, sex-, and antiplatelet therapy-matched controls who had not had an IS in the previous 6 months. METHODS: We compared the frequency of aspirin therapy discontinuation during the 4 weeks before an ischemic cerebral event in patients and the 4 weeks before interview in controls. RESULTS: The 2 groups had a similar frequency of risk factors, except for coronary heart disease, which was more frequent in patients (36% vs 18%; P < .001). Aspirin use had been discontinued in 13 patients and 4 controls. Aspirin interruption yielded an odds ratio for IS/transient ischemic attack of 3.4 (95% confidence interval, 1.08-10.63; P < .005) after adjustment in a multivariable model. CONCLUSIONS: These results highlight the importance of aspirin therapy compliance and give an estimate of the risk associated with the discontinuation of aspirin therapy in patients at risk for IS, particularly those with coronary heart disease.

Posterior cerebral artery infarction from middle cerebral artery infarction.

BACKGROUND: While it is known that posterior cerebral artery (PCA) infarction may simulate middle cerebral artery (MCA) infarction, the frequency and localization of this occurrence are unknown. OBJECTIVE: To determine the frequency of PCA infarction mimicking MCA infarction and the territory of the PCA most commonly involved in this simulation. DESIGN: We studied 202 patients with isolated infarction in the PCA admitted to our stroke center to determine the frequency of PCA infarction simulating MCA infarction, the involved PCA territory, and the patterns of clinical presentation. RESULTS: We found 36 patients (17.8%) with PCA ischemic stroke who had clinical features suggesting MCA stroke. The PCA territory most commonly involved was the superficial PCA territory (66.7%), followed by the proximal PCA territory (16.7%) and both the proximal and the superficial PCA territories (16.7%). The principal stroke mechanism was cardioembolic (54.1%) in the superficial PCA territory, lacunar (46.2%) in the proximal PCA territory, and undetermined (40.2%) in both the proximal and the superficial territories. Among the 36 patients, the most common clinical associations were aphasia (13 patients), visuospatial neglect (13 patients), and severe hemiparesis (7 patients). CONCLUSIONS: Posterior cerebral artery infarction simulating MCA infarction is more common than previously thought. Early recognition of the different stroke subtypes in these 2 arteries may allow specific management.

Clopidogrel: cardiologists' panacea or neurologists' headache?

Clopidogrel (Plavix) is a potent platelet inhibitor that has been demonstrated to be significantly more effective than aspirin for the prevention of atherothrombotic events in patients with established atherosclerotic disease in the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) study. Furthermore, the benefit of clopidogrel compared with placebo in patients with acute coronary syndromes, as well as those undergoing percutaneous coronary intervention receiving a standard therapy including aspirin, has been largely demonstrated by the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE), Clopidogrel for the Reduction of Events During Observation (CREDO), CLopidogrel as Adjunctive ReperfusIon TherapY-Thrombolysis In Myocardial Infarction (CLARITY-TIMI)28, and Clopidogrel and Metoprolol in Myocardial Infarction Trial/Secon Chinese Cardiac Study (COMMIT/CCS-2) trials. However, in the Management of Atherothrombosis with Clopidogrel in High-risk patients with recent transient ischemic attack or ischemic stroke (MATCH) trial, there was no clinical benefit of adding aspirin versus placebo to a standard therapy of clopidogrel in patients with cerebrovascular disease. The implications of these findings, as well as future perspectives from upcoming trials, shall be discussed herein.