Rivaroxaban versus aspirin for prevention of covert brain infarcts in patients with embolic stroke of undetermined source: NAVIGATE ESUS MRI substudy

Rivaroxabán; Aspirina; Infart cerebralRivaroxabán; Aspirina; Infarto cerebralRivaroxabán; Aspirin; Brain infarctBackground: Covert brain infarcts are associated with important neurological morbidity. Their incidence in patients with embolic stroke of undetermined source (ESUS) is unknown. Aims: To assess the incidence of covert brain infarcts and cerebral microbleeds using MRI in a prospective substudy of the NAVIGATE ESUS randomized trial and to evaluate the effects of antithrombotic therapies. Methods: At 87 sites in 15 countries, substudy participants were randomly assigned to receive rivaroxaban 15 mg daily or aspirin 100 mg daily and underwent brain MRI near randomization and after study termination. The primary outcome was incident brain infarct (clinical ischemic stroke or covert brain infarct). Brain infarcts and microbleeds were ascertained centrally by readers unaware of treatment. Treatment effects were estimated using logistic regression. Results: Among the 718 substudy participants with interpretable, paired MRIs, the mean age was 67 years and 61% were men with a median of 52 days between the qualifying ischemic stroke and randomization and a median of seven days between randomization and baseline MRI. During the median (IQR) 11 (12) month interval between scans, clinical ischemic strokes occurred in 27 (4%) participants, while 60 (9%) of the remaining participants had an incident covert brain infarct detected by MRI. Assignment to rivaroxaban was not associated with reduction in the incidence of brain infarct (OR 0.77, 95% CI 0.49, 1.2) or of covert brain infarct among those without clinical stroke (OR 0.85, 95% CI 0.50, 1.4). New microbleeds were observed in 7% and did not differ among those assigned rivaroxaban vs. aspirin (HR 0.95, 95% CI 0.52-1.7). Conclusions: Incident covert brain infarcts occurred in twice as many ESUS patients as a clinical ischemic stroke. Treatment with rivaroxaban compared with aspirin did not significantly reduce the incidence of covert brain infarcts or increase the incidence of microbleeds, but the confidence intervals for treatment effects were wide.Registration: https://www.clinicaltrials.gov. Unique identifier: NCT02313909.The NAVIGATE ESUS trial and the MRI Substudy were sponsored by Bayer AG

Sex Differences in rt-PA Utilization at Hospitals Treating Stroke: The National Inpatient Sample.

BACKGROUND AND PURPOSE: Sex and race disparities in recombinant tissue plasminogen activator (rt-PA) use have been reported. We sought to explore sex and race differences in the utilization of rt-PA at primary stroke centers (PSCs) compared to non-PSCs across the US. METHODS: Data from the National (Nationwide) Inpatient Sample (NIS) 2004-2010 was utilized to assess sex differences in treatment for ischemic stroke in PSCs compared to non-PSCs. RESULTS: There were 304,152 hospitalizations with a primary diagnosis of ischemic stroke between 2004 and 2010 in the analysis: 75,160 (24.7%) patients were evaluated at a PSC. A little over half of the patients evaluated at PSCs were female (53.8%). A lower proportion of women than men received rt-PA at both PSCs (6.8 vs. 7.5%, p \u3c 0.001) and non-PSCs (2.3 vs. 2.8%, p \u3c 0.001). After adjustment for potential confounders the odds of being treated with rt-PA remained lower for women regardless of presentation to a PSC (OR 0.87, 95% CI 0.81-0.94) or non-PSC (OR 0.88, 95% CI 0.82-0.94). After stratifying by sex and race, the lowest absolute treatment rates were observed in black women (4.4% at PSC, 1.9% at non-PSC). The odds of treatment, relative to white men, was however lowest for white women (PSC OR = 0.85, 95% CI 0.78-0.93; non-PSC OR = 0.80, 95% CI 0.75-0.85). In the multivariable model, sex did not modify the effect of PSC certification on rt-PA utilization (p-value for interaction = 0.58). CONCLUSION: Women are less likely to receive rt-PA than men at both PSCs and non-PSCs. Absolute treatment rates are lowest in black women, although the relative difference in men and women was greatest for white women

Sex Differences in rt-PA Utilization at Hospitals Treating Stroke: The National Inpatient Sample

Background and purposeSex and race disparities in recombinant tissue plasminogen activator (rt-PA) use have been reported. We sought to explore sex and race differences in the utilization of rt-PA at primary stroke centers (PSCs) compared to non-PSCs across the US.MethodsData from the National (Nationwide) Inpatient Sample (NIS) 2004–2010 was utilized to assess sex differences in treatment for ischemic stroke in PSCs compared to non-PSCs.ResultsThere were 304,152 hospitalizations with a primary diagnosis of ischemic stroke between 2004 and 2010 in the analysis: 75,160 (24.7%) patients were evaluated at a PSC. A little over half of the patients evaluated at PSCs were female (53.8%). A lower proportion of women than men received rt-PA at both PSCs (6.8 vs. 7.5%, p < 0.001) and non-PSCs (2.3 vs. 2.8%, p < 0.001). After adjustment for potential confounders the odds of being treated with rt-PA remained lower for women regardless of presentation to a PSC (OR 0.87, 95% CI 0.81–0.94) or non-PSC (OR 0.88, 95% CI 0.82–0.94). After stratifying by sex and race, the lowest absolute treatment rates were observed in black women (4.4% at PSC, 1.9% at non-PSC). The odds of treatment, relative to white men, was however lowest for white women (PSC OR = 0.85, 95% CI 0.78–0.93; non-PSC OR = 0.80, 95% CI 0.75–0.85). In the multivariable model, sex did not modify the effect of PSC certification on rt-PA utilization (p-value for interaction = 0.58).ConclusionWomen are less likely to receive rt-PA than men at both PSCs and non-PSCs. Absolute treatment rates are lowest in black women, although the relative difference in men and women was greatest for white women

Rivaroxaban versus aspirin for prevention of covert brain infarcts in patients with embolic stroke of undetermined source: NAVIGATE ESUS MRI substudy

Background: Covert brain infarcts are associated with important neurological morbidity. Their incidence in patients with embolic stroke of undetermined source (ESUS) is unknown. Aims: To assess the incidence of covert brain infarcts and cerebral microbleeds using MRI in a prospective substudy of the NAVIGATE ESUS randomized trial and to evaluate the effects of antithrombotic therapies. Methods: At 87 sites in 15 countries, substudy participants were randomly assigned to receive rivaroxaban 15 mg daily or aspirin 100 mg daily and underwent brain MRI near randomization and after study termination. The primary outcome was incident brain infarct (clinical ischemic stroke or covert brain infarct). Brain infarcts and microbleeds were ascertained centrally by readers unaware of treatment. Treatment effects were estimated using logistic regression. Results: Among the 718 substudy participants with interpretable, paired MRIs, the mean age was 67 years and 61% were men with a median of 52 days between the qualifying ischemic stroke and randomization and a median of seven days between randomization and baseline MRI. During the median (IQR) 11 (12) month interval between scans, clinical ischemic strokes occurred in 27 (4%) participants, while 60 (9%) of the remaining participants had an incident covert brain infarct detected by MRI. Assignment to rivaroxaban was not associated with reduction in the incidence of brain infarct (OR 0.77, 95% CI 0.49, 1.2) or of covert brain infarct among those without clinical stroke (OR 0.85, 95% CI 0.50, 1.4). New microbleeds were observed in 7% and did not differ among those assigned rivaroxaban vs. aspirin (HR 0.95, 95% CI 0.52–1.7). Conclusions: Incident covert brain infarcts occurred in twice as many ESUS patients as a clinical ischemic stroke. Treatment with rivaroxaban compared with aspirin did not significantly reduce the incidence of covert brain infarcts or increase the incidence of microbleeds, but the confidence intervals for treatment effects were wide. Registration: https://www.clinicaltrials.gov. Unique identifier: NCT 02313909

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Bow hunter\u27s syndrome caused by accessory cervical ossification: posterolateral decompression and the use of intraoperative Doppler ultrasonography.

BACKGROUND: Bow hunter\u27s syndrome refers to symptomatic vertebrobasilar insufficiency provoked by physiologic head rotation. CASE DESCRIPTION: We report a unique case of bow hunter\u27s syndrome caused by an accessory cervical ossification and the first use of intraoperative Doppler ultrasonography directly upon the vertebral artery during the surgical repair. After a traumatic motor-vehicle collision, the patient developed recurrent syncopal episodes when he turned his head abruptly to the right. Transcranial Doppler studies and vertebral angiography with the patient\u27s neck rotated into the symptomatic position revealed marked reduction of vertebral artery flow, and fine-cut CT of the upper cervical spine demonstrated the compressive accessory ossicle. Intraoperative Doppler ultrasound performed with the head in neutral and rotated positions, before and after surgical decompression, demonstrated restoration of blood flow in the vertebral artery. We discuss the mechanisms of bow hunter\u27s syndrome and the advantages of intraoperative Doppler ultrasonography. CONCLUSION: This case describes the first use of intraoperative Doppler ultrasonography directly upon the vertebral artery to provide an unrestricted real-time assessment of the surgical decompression for bow hunter\u27s syndrome

Stroke pathophysiology, diagnosis, and management

Some accessibility features are available on the Science Direct platform, including compatible HTML and PDF book chapters and journal articles. Authored by the world's foremost stroke experts, this classic text brings you fully up to date with current research findings and management approaches for cerebrovascular disease. Stroke: Pathophysiology, Diagnosis, and Management, 7th Edition, covers every aspect of this fast-moving field, and is an ideal resource for stroke specialists, general neurologists, and other medical professionals with an interest in stroke. You'll find expert clinical guidance, comprehensive pathophysiology coverage, data from recent trials, advances in diagnostic tests, full-color CT images, pathology slides, and much more, for a complete picture of today's stroke medicine. Helps you recognize the clinical manifestations of stroke, use the latest laboratory and imaging studies to arrive at a diagnosis, and generate an effective medical and surgical treatment plan. Keeps you abreast of the overwhelming volume of studies and guidelines in this dynamic field, providing clear summaries and practical evaluations of all relevant data. Contains updates throughout, including the latest clinical trials (thrombectomy, DAWN, DEFUSE), genetics research, prevention research, new therapies, and the new guidelines from the ASA. Includes new slides for lectures, covering basic science, case studies, and interventional treatment overviews. Features a Key Points summary at the beginning of each chapter so you can quickly find important information. Provides abundant full-color CT images and pathology slides that help you make efficient and accurate diagnoses. Enhanced eBook version included with purchase. Your enhanced eBook allows you to access all of the text, figures, and references from the book on a variety of devices

Prevention of Stroke in Patients With Silent Cerebrovascular Disease : A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

Two decades of epidemiological research shows that silent cerebrovascular disease is common and is associated with future risk for stroke and dementia. It is the most common incidental finding on brain scans. To summarize evidence on the diagnosis and management of silent cerebrovascular disease to prevent stroke, the Stroke Council of the American Heart Association convened a writing committee to evaluate existing evidence, to discuss clinical considerations, and to offer suggestions for future research on stroke prevention in patients with 3 cardinal manifestations of silent cerebrovascular disease: silent brain infarcts, magnetic resonance imaging white matter hyperintensities of presumed vascular origin, and cerebral microbleeds. The writing committee found strong evidence that silent cerebrovascular disease is a common problem of aging and that silent brain infarcts and white matter hyperintensities are associated with future symptomatic stroke risk independently of other vascular risk factors. In patients with cerebral microbleeds, there was evidence of a modestly increased risk of symptomatic intracranial hemorrhage in patients treated with thrombolysis for acute ischemic stroke but little prospective evidence on the risk of symptomatic hemorrhage in patients on anticoagulation. There were no randomized controlled trials targeted specifically to participants with silent cerebrovascular disease to prevent stroke. Primary stroke prevention is indicated in patients with silent brain infarcts, white matter hyperintensities, or microbleeds. Adoption of standard terms and definitions for silent cerebrovascular disease, as provided by prior American Heart Association/American Stroke Association statements and by a consensus group, may facilitate diagnosis and communication of findings from radiologists to clinicians

Prevention of Stroke in Patients With Silent Cerebrovascular Disease : A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

Two decades of epidemiological research shows that silent cerebrovascular disease is common and is associated with future risk for stroke and dementia. It is the most common incidental finding on brain scans. To summarize evidence on the diagnosis and management of silent cerebrovascular disease to prevent stroke, the Stroke Council of the American Heart Association convened a writing committee to evaluate existing evidence, to discuss clinical considerations, and to offer suggestions for future research on stroke prevention in patients with 3 cardinal manifestations of silent cerebrovascular disease: silent brain infarcts, magnetic resonance imaging white matter hyperintensities of presumed vascular origin, and cerebral microbleeds. The writing committee found strong evidence that silent cerebrovascular disease is a common problem of aging and that silent brain infarcts and white matter hyperintensities are associated with future symptomatic stroke risk independently of other vascular risk factors. In patients with cerebral microbleeds, there was evidence of a modestly increased risk of symptomatic intracranial hemorrhage in patients treated with thrombolysis for acute ischemic stroke but little prospective evidence on the risk of symptomatic hemorrhage in patients on anticoagulation. There were no randomized controlled trials targeted specifically to participants with silent cerebrovascular disease to prevent stroke. Primary stroke prevention is indicated in patients with silent brain infarcts, white matter hyperintensities, or microbleeds. Adoption of standard terms and definitions for silent cerebrovascular disease, as provided by prior American Heart Association/American Stroke Association statements and by a consensus group, may facilitate diagnosis and communication of findings from radiologists to clinicians