Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may ...result in a lower risk of recurrent stroke than aspirin.
We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source. The primary efficacy outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis; the primary safety outcome was the rate of major bleeding.
A total of 7213 participants were enrolled at 459 sites; 3609 patients were randomly assigned to receive rivaroxaban and 3604 to receive aspirin. Patients had been followed for a median of 11 months when the trial was terminated early because of a lack of benefit with regard to stroke risk and because of bleeding associated with rivaroxaban. The primary efficacy outcome occurred in 172 patients in the rivaroxaban group (annualized rate, 5.1%) and in 160 in the aspirin group (annualized rate, 4.8%) (hazard ratio, 1.07; 95% confidence interval CI, 0.87 to 1.33; P=0.52). Recurrent ischemic stroke occurred in 158 patients in the rivaroxaban group (annualized rate, 4.7%) and in 156 in the aspirin group (annualized rate, 4.7%). Major bleeding occurred in 62 patients in the rivaroxaban group (annualized rate, 1.8%) and in 23 in the aspirin group (annualized rate, 0.7%) (hazard ratio, 2.72; 95% CI, 1.68 to 4.39; P<0.001).
Rivaroxaban was not superior to aspirin with regard to the prevention of recurrent stroke after an initial embolic stroke of undetermined source and was associated with a higher risk of bleeding. (Funded by Bayer and Janssen Research and Development; NAVIGATE ESUS ClinicalTrials.gov number, NCT02313909 .).
To examine whether antiplatelet medication use at onset of intracerebral hemorrhage (ICH) is associated with hemorrhage growth and outcome after spontaneous ICH using a large, prospectively collected ...database from a recent clinical trial.
The Cerebral Hemorrhage and NXY-059 Treatment trial was a randomized, placebo-controlled trial of NXY-059 after spontaneous ICH. We analyzed patients in the placebo arm, and correlated antiplatelet medication use at the time of ICH with initial ICH volumes, ICH growth in the first 72 hours, and modified Rankin Score at 90 days. Patients on oral anticoagulation were excluded.
There were 282 patients included in this analysis, including 70 (24.8%) who were taking antiplatelet medications at ICH onset. Use of antiplatelet medications at ICH onset had no association with the volume of ICH at presentation, growth of ICH at 72 hours, initial edema volume, or edema growth. In multivariable analysis, there was no association of use of antiplatelet medications with any hemorrhage expansion (relative risk RR 0.85 upper limit of confidence interval (UCI) 1.03, p = 0.16), hemorrhage expansion greater than 33% (RR 0.77 UCI 1.18, p = 0.32), or clinical outcome at 90 days (odds ratio 0.67, 95% confidence interval 0.39-1.14, p = 0.14).
Use of antiplatelet medications at intracerebral hemorrhage (ICH) onset is not associated with increased hemorrhage volumes, hemorrhage expansion, or clinical outcome at 90 days. These findings suggest that attempts to reverse antiplatelet medications after ICH may not be warranted.
To investigate whether cervical carotid artery dissection (CCAD) is associated with anatomic characteristics of the styloid process of the temporal bone.
CT angiograms from 38 case patients with CCAD ...and 38 age- and sex-matched control subjects without dissection were studied. Styloid process length, angulation in the axial and rostral-caudal planes, and proximity to the carotid artery were measured bilaterally by raters blinded to radiology reports and clinical information.
In control subjects, there was substantial variation in styloid process length (range 4.6-42.9 mm), medial angulation (range 16-89°), caudal angulation (range 31-80°), and proximity to the carotid (range 0.7-15.4 mm). Control subjects also demonstrated marked symmetry between sides (correlation coefficients 0.80 for length, 0.34 for proximity, 0.81 for medial angulation, and 0.87 for caudal angulation). In case patients, the mean styloid length on the side of the dissection was not significantly longer than that on the contralateral side (mean 30.3 vs 29.7 mm, p = 0.30). The styloid process was significantly longer ipsilateral to the dissection in case patients compared with the side-matched process in control subjects (mean 30.3 vs 26.6 mm, p = 0.03). Carotid dissection was associated with increasing styloid process length (OR OR 1.08/mm, 95% confidence interval CI 1.002-1.17, p = 0.04). The OR of dissection in the highest quartile of length compared with that in the lower 3 quartiles was 4.0 (95% CI 1.3-14.2, p = 0.03).
CCAD is associated with a longer styloid process, suggesting that mechanical injury from the styloid may contribute to the pathogenesis of CCAD.
No single outcome measure can describe or predict all dimensions of recovery and disability after acute stroke. Several scales have proven reliability and validity in stroke trials, including the ...National Institutes of Health stroke scale (NIHSS), the modified Rankin scale (mRS), the Barthel index (BI), the Glasgow outcome scale (GOS), and the stroke impact scale (SIS). Several scales have been combined in stroke trials to derive a global statistic to better define the effect of acute interventions, although this composite statistic is not clinically tenable. In practice, the NIHSS is useful for early prognostication and serial assessment, whereas the BI is useful for planning rehabilitative strategies. The mRS and GOS provide summary measures of outcome and might be most relevant to clinicians and patients considering early intervention. The SIS was designed to measure the patient's perspective on the effect of stroke. Familiarity with these scales could improve clinicians' interpretation of stroke research and their clinical decision-making.
Antithrombotic therapy for intracranial arterial stenosis was recently evaluated in the Warfarin versus Aspirin for Symptomatic Intracranial Disease (WASID) trial. A prespecified aim of WASID was to ...identify patients at highest risk for stroke in the territory of the stenotic artery who would be the target group for a subsequent trial comparing intracranial stenting with medical therapy.
WASID was a randomized, double-blinded, multicenter trial involving 569 patients with transient ischemic attack or ischemic stroke due to 50% to 99% stenosis of a major intracranial artery. Median time from qualifying event to randomization was 17 days, and mean follow-up was 1.8 years. Multivariable Cox proportional hazards models were used to identify factors associated with subsequent ischemic stroke in the territory of the stenotic artery. Subsequent ischemic stroke occurred in 106 patients (19.0%); 77 (73%) of these strokes were in the territory of the stenotic artery. Risk of stroke in the territory of the stenotic artery was highest with severe stenosis > or =70% (hazard ratio 2.03; 95% confidence interval 1.29 to 3.22; P=0.0025) and in patients enrolled early (< or =17 days) after the qualifying event (hazard ratio 1.69; 95% confidence interval 1.06 to 2.72; P=0.028). Women were also at increased risk, although this was of borderline significance (hazard ratio 1.59; 95% confidence interval 1.00 to 2.55; P=0.051). Location of stenosis, type of qualifying event, and prior use of antithrombotic medications were not associated with increased risk.
Among patients with symptomatic intracranial stenosis, the risk of subsequent stroke in the territory of the stenotic artery is greatest with stenosis > or =70%, after recent symptoms, and in women.
The efficacy of closure of a patent foramen ovale (PFO) in the prevention of recurrent stroke after cryptogenic stroke is uncertain. We investigated the effect of PFO closure combined with ...antiplatelet therapy versus antiplatelet therapy alone on the risks of recurrent stroke and new brain infarctions.
In this multinational trial involving patients with a PFO who had had a cryptogenic stroke, we randomly assigned patients, in a 2:1 ratio, to undergo PFO closure plus antiplatelet therapy (PFO closure group) or to receive antiplatelet therapy alone (antiplatelet-only group). Imaging of the brain was performed at the baseline screening and at 24 months. The coprimary end points were freedom from clinical evidence of ischemic stroke (reported here as the percentage of patients who had a recurrence of stroke) through at least 24 months after randomization and the 24-month incidence of new brain infarction, which was a composite of clinical ischemic stroke or silent brain infarction detected on imaging.
We enrolled 664 patients (mean age, 45.2 years), of whom 81% had moderate or large interatrial shunts. During a median follow-up of 3.2 years, clinical ischemic stroke occurred in 6 of 441 patients (1.4%) in the PFO closure group and in 12 of 223 patients (5.4%) in the antiplatelet-only group (hazard ratio, 0.23; 95% confidence interval CI, 0.09 to 0.62; P=0.002). The incidence of new brain infarctions was significantly lower in the PFO closure group than in the antiplatelet-only group (22 patients 5.7% vs. 20 patients 11.3%; relative risk, 0.51; 95% CI, 0.29 to 0.91; P=0.04), but the incidence of silent brain infarction did not differ significantly between the study groups (P=0.97). Serious adverse events occurred in 23.1% of the patients in the PFO closure group and in 27.8% of the patients in the antiplatelet-only group (P=0.22). Serious device-related adverse events occurred in 6 patients (1.4%) in the PFO closure group, and atrial fibrillation occurred in 29 patients (6.6%) after PFO closure.
Among patients with a PFO who had had a cryptogenic stroke, the risk of subsequent ischemic stroke was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone; however, PFO closure was associated with higher rates of device complications and atrial fibrillation. (Funded by W.L. Gore and Associates; Gore REDUCE ClinicalTrials.gov number, NCT00738894 .).
There are limited data on the relationship between patient and site characteristics and clinical outcomes after intracranial stenting.
We performed a multivariable analysis that correlated patient ...and site characteristics with the occurrence of the primary endpoint (any stroke or death within 30 days of stenting or stroke in the territory of the stented artery beyond 30 days) in 160 patients enrolled in this stenting registry. All patients presented with an ischemic stroke, TIA, or other cerebral ischemic event (e.g., vertebrobasilar insufficiency) in the territory of a suspected 50-99% stenosis of a major intracranial artery while on antithrombotic therapy.
Cerebral angiography confirmed that 99% (158/160) of patients had a 50-99% stenosis. In multivariable analysis, the primary endpoint was associated with posterior circulation stenosis (vs anterior circulation) (hazard ratio HR 3.4, 95% confidence interval CI 1.2-9.3, p = 0.018), stenting at low enrollment sites (< 10 patients each) (vs high enrollment site) (HR 2.8, 95% CI 1.1-7.6, p = 0.038), < or = 10 days from qualifying event to stenting (vs > or = 10 days) (HR 2.7, 95% CI 1.0-7.8, p = 0.058), and stroke as a qualifying event (vs TIA/other) (HR 3.2, 95% CI 0.9-11.2, p = 0.064). There was no significant difference in the primary endpoint based on age, gender, race, or percent stenosis (50-69% vs 70-99%).
Major cerebrovascular complications after intracranial stenting may be associated with posterior circulation stenosis, low volume sites, stenting soon after a qualifying event, and stroke as the qualifying event. These factors will need to be monitored in future trials of intracranial stenting.
1) To evaluate the risk of subsequent stroke or death in patients with a cryptogenic stroke and a patent foramen ovale (PFO), atrial septal aneurysm (ASA), or both. 2) To establish the optimal method ...of stroke prevention in this population of patients.
MEDLINE, the Cochrane database of systematic reviews, key meeting abstracts from 1997 to 2002, and relevant reference lists were searched to select studies that prospectively collected outcome data in cryptogenic stroke patients with and without interatrial septal abnormalities. Studies were also selected that prospectively compared at least two treatment options. The quality of each study was graded (class I to IV) using a standard classification-of-evidence scheme for each question. Risk analyses were performed and data were pooled when appropriate.
The literature search generated 129 articles of which only four fulfilled the inclusion and exclusion criteria. Two studies were graded class I, one study was graded class II, and one study was graded class IV for prognosis. Pooled results of the two class I and one class II studies demonstrated no increased risk of subsequent stroke or death in patients with PFO compared to those without (RR = 0.95, 95% CI 0.62 to 1.44). One class I study found increased risk of recurrent stroke in patients with PFO and ASA (annual rate = 3.8% versus 1.05%, RR = 2.98, 95% CI 1.17 to 7.58) but not increased risk of a composite of stroke and death (annual rate = 3.8% versus 1.8%, RR = 2.10, 95% CI 0.86 to 5.06). Regarding therapy, one study was graded class II, one study class III, and two studies class IV. Among patients with cryptogenic stroke and PFO or ASA, there was no significant difference in stroke or death rate in warfarin-treated patients relative to aspirin-treated patients and the confidence intervals were unable to rule out a benefit of one drug over the other (annual rate = 4.7% versus 8.9%, RR = 0.53, 95% CI 0.18 to 1.58). Minor bleeding rates were higher in the cohort of patients who received warfarin (22.9/100 patient-years versus 8.66/100 patient-years, rate ratio = 2.64, p < 0.001). No studies compared medical therapy with surgical or endovascular closure.
PFO is not associated with increased risk of subsequent stroke or death among medically treated patients with cryptogenic stroke. However, both PFO and ASA possibly increase the risk of subsequent stroke (but not death) in medically treated patients younger than 55 years. In patients with a cryptogenic stroke and an atrial septal abnormality the evidence is insufficient to determine if warfarin or aspirin is superior in preventing recurrent stroke or death, but minor bleeding is more frequent with warfarin. There is insufficient evidence to evaluate the efficacy of surgical or endovascular closure.
Large‐scale measurements of the spatial distribution of water content in soils and snow are challenging for state‐of‐the‐art hydrogeophysical methods. Cosmic‐ray neutron sensing (CRNS) is a ...noninvasive technology that has the potential to bridge the scale gap between conventional in situ sensors and remote sensing products in both, horizontal and vertical domains. In this study, we explore the feasibility and potential of estimating water content in soils and snow with neutron detectors in moving trains. Theoretical considerations quantify the stochastic measurement uncertainty as a function of water content, altitude, resolution, and detector efficiency. Numerical experiments demonstrate that the sensitivity of measured water content is almost unperturbed by train materials. Finally, three distinct real‐world experiments provide a proof of concept on short and long‐range tracks. With our results a transregional observational soil moisture product becomes a realistic vision within the next years.
Plain Language Summary
Large‐scale measurements of the spatial distribution of water content in soils and snow are challenging for state‐of‐the‐art hydrogeophysical methods. Cosmic‐ray neutron sensing (CRNS) is a mobile and noninvasive technology that has the potential to bridge the scale gap between conventional in situ sensors and satellite measurements in both, the horizontal and the vertical domain. In this study, we explore the feasibility and potential of estimating water content in soils or snow with neutron detectors in trains. Theoretical considerations estimate how train velocity and recording period influence the uncertainty of such measurements and demonstrate that train materials hardly affect the neutron response to water content. Three distinct experiments provide a proof of concept on short and long‐range tracks. With our results, a transregional observational soil moisture product becomes a realistic vision within the next years.
Key Points
Cosmic‐ray neutron detectors in trains respond to spatial patterns of water content
First experiments and analysis provide a proof of concept
Using the railway system for regular environmental monitoring could extend the measurement capability to transregional and nationwide scales
There are limited data on the relationship between control of vascular risk factors and vascular events in patients with symptomatic intracranial arterial stenosis.
We utilized the Warfarin Aspirin ...Symptomatic Intracranial Disease study database to analyze vascular and lifestyle risk factors at baseline and averaged over the course of the trial. Cutoff levels defining good control for each factor were prespecified based on national guidelines. Endpoints evaluated included 1) ischemic stroke, myocardial infarction, or vascular death or 2) ischemic stroke alone. Univariate associations were assessed using the log-rank test and multivariable analysis was done using Cox proportional hazards regression.
From baseline until year 2 follow-up, there was not a significant improvement in blood pressure control. During the same period, there were improvements in patients with total cholesterol <200 mg/dL (54.6% to 79.2%, p < 0.001) or low-density lipoprotein <100 mg/dL (28.7% to 55.9%, p < 0.001). Multivariable analysis showed that systolic blood pressure >or=140 mm Hg (HR = 1.79, p = 0.0009, 95% confidence limits 1.27 to 2.52), no alcohol consumption (HR 1.69, 1.21 to 2.39, p = 0.002), and cholesterol >or=200 mg/dL (HR 1.44, 1.004 to 2.07, p = 0.048) were associated with an increased risk of stroke, myocardial infarction, or vascular death. The same risk factors were predictors of ischemic stroke alone in multivariable analysis.
Elevated blood pressure and cholesterol levels in symptomatic patients with intracranial stenosis are associated with an increased risk of stroke and other major vascular events.
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