Ameliorating Racial Disparities in Vascular Risk Factor Management With Aggressive Medical Management in the SAMMPRIS Trial.

BACKGROUND: The WASID trial (Warfarin-Aspirin Symptomatic Intracranial Disease) and the SAMMPRIS trial (Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis) evaluated optimal management of symptomatic intracranial atherosclerotic stenosis. The aim of this retrospective, observational study was to determine whether aggressive medical management used in the SAMMPRIS trial ameliorated disparities in risk factor control between Black and non-Black patients. METHODS: The SAMMPRIS trial was a randomized controlled trial that enrolled patients with symptomatic intracranial atherosclerotic stenosis between November 2008 and April 2011. The frequency of risk factors at study entry (baseline) and mean levels of systolic blood pressure, diastolic blood pressure, LDL (low-density lipoprotein), hemoglobin A1c, and exercise level (quantified by physician-based assessment and counseling for exercise score) at baseline and at 1 year of follow-up were compared between Black (n=104) versus non-Black patients (n=347). RESULTS: Significant differences at baseline in Black patients (listed first) versus non-Black patients were age (57.5 versus 61.0 years; P=0.004), hypertension (95.2% versus 87.5%; P=0.027), diabetes (52.9% versus 39.7%; P=0.017), mean diastolic blood pressure (82.4 versus 79.5 mm Hg; P=0.035), and mean physician-based assessment and counseling for exercise score (2.7 versus 3.3; P=0.002). The mean diastolic blood pressure and mean physician-based assessment and counseling for exercise scores at 1 year in Black versus non-Black patients were 74.7 versus 75.5 mm Hg (P=0.575) and 4.2 versus 4.1 (P=0.593), respectively. No disparities in other modifiable risk factors emerged at 1 year. CONCLUSIONS: Significant differences in important risk factors (physical activity and diastolic blood pressure) at baseline between Black and non-Black patients resolved at 1 year, suggesting that aggressive medical management may have an important role in ameliorating disparities in risk factor control between Black and non-Black patients.

Chronic remote ischaemic conditioning in patients with symptomatic intracranial atherosclerotic stenosis (the RICA trial): a multicentre, randomised, double-blind sham-controlled trial in China.

BACKGROUND: Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of stroke worldwide, and it is associated with a high risk of recurrent stroke with currently recommended treatments. We aimed to evaluate the effect of chronic remote ischaemic conditioning on prevention of ischaemic events in patients with symptomatic ICAS. METHODS: The RICA trial is a multicentre, randomised, double-blind, sham-controlled trial at 84 stroke centres in China. Patients aged 40-80 years with ischaemic stroke or transient ischaemic attack attributable to angiographically verified 50-99% stenosis of a major intracranial artery were randomly assigned (1:1), via an interactive web-based system by computer-generated randomisation code, to either remote ischaemic conditioning or sham remote ischaemic conditioning once daily for 12 months and voluntarily thereafter. All investigators and patients were masked to treatment allocation. The primary efficacy endpoint was the time to first occurrence of non-fatal or fatal ischaemic stroke, with survival analysed by the Kaplan-Meier method. Primary and safety analyses were done in the intention-to-treat population. The RICA trial is registered with ClinicalTrials.gov, number NCT02534545. FINDINGS: Between Oct 28, 2015, and Feb 28, 2019, 3033 patients were enrolled and randomly assigned to either remote ischaemic conditioning (n=1517; intervention group) or sham remote ischaemic conditioning (n=1516; sham group). Median follow-up was 3·5 years (IQR 2·7-4·4). A non-fatal or fatal ischaemic stroke occurred in 257 (16·9%) patients in the intervention group compared with 288 (19·0%) patients in sham group. There was no difference in the survival distribution for time to first occurrence of non-fatal or fatal ischaemic stroke (hazard ratio 0·87, 95% CI 0·74-1·03; p=0·12). In the intervention group, 79 (5·2%) patients died from any cause, and in the sham group, 84 (5·5%) patients died from any cause (hazard ratio 0·93, 95% CI 0·68-1·27; p=0·65). No intervention-related serious adverse events were observed. INTERPRETATION: No evidence was found for a difference between remote ischaemic conditioning and sham remote ischaemic conditioning in lowering the risk of ischaemic stroke in patients with symptomatic ICAS. The benefit of remote ischaemic conditioning might have been diluted by poor compliance. Future studies of remote ischaemic conditioning in this population should address challenges in patients' compliance and assess longer term treatment. FUNDING: Ministry of Science and Technology China, Beijing Municipal Education Commission, Beijing Municipal Finance Bureau. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Stroke Prevention in Symptomatic Large Artery Intracranial Atherosclerosis Practice Advisory: Report of the AAN Guideline Subcommittee.

BACKGROUND AND OBJECTIVES: To review treatments for reducing the risk of recurrent stroke or death in patients with symptomatic intracranial atherosclerotic arterial stenosis (sICAS). METHODS: The development of this practice advisory followed the process outlined in the American Academy of Neurology Clinical Practice Guideline Process Manual, 2011 Edition, as amended. The systematic review included studies through November 2020. Recommendations were based on evidence, related evidence, principles of care, and inferences. MAJOR RECOMMENDATIONS: Clinicians should recommend aspirin 325 mg/d for long-term prevention of stroke and death and should recommend adding clopidogrel 75 mg/d to aspirin for up to 90 days to further reduce stroke risk in patients with severe (70%-99%) sICAS who have low risk of hemorrhagic transformation. Clinicians should recommend high-intensity statin therapy to achieve a goal low-density lipoprotein cholesterol level <70 mg/dL, a long-term blood pressure target of <140/90 mm Hg, at least moderate physical activity, and treatment of other modifiable vascular risk factors for patients with sICAS. Clinicians should not recommend percutaneous transluminal angioplasty and stenting for stroke prevention in patients with moderate (50%-69%) sICAS or as the initial treatment for stroke prevention in patients with severe sICAS. Clinicians should not routinely recommend angioplasty alone or indirect bypass for stroke prevention in patients with sICAS outside clinical trials. Clinicians should not recommend direct bypass for stroke prevention in patients with sICAS. Clinicians should counsel patients about the risks of percutaneous transluminal angioplasty and stenting and alternative treatments if one of these procedures is being contemplated.

Intracranial atherosclerotic stenosis: risk factors, diagnosis, and treatment.

Intracranial atherosclerotic stenosis (ICAS) is one of the most frequent causes of stroke worldwide and confers one of the greatest risks of recurrent stroke compared with other causes of stroke. Asymptomatic ICAS is increasingly recognised as a risk factor for silent brain infarctions and dementia, magnifying the global burden of ICAS. Although ICAS is a lumen-based diagnosis, newer diagnostic imaging techniques, such as high-resolution MRI, might help to identify high-risk population subgroups to test interventions that might reduce the risk of stroke recurrence. Secondary stroke prevention in patients with ICAS currently consists of intensive management of modifiable risk factors and dual antiplatelet therapy, which is subsequently reduced to aspirin alone. Despite these therapies, the risk of recurrent stroke in patients presenting with stroke related to 70-99% ICAS exceeds 20% at 1 year; as such, better therapies are urgently needed. The optimal duration and combination of dual antiplatelet therapy in patients with ICAS is uncertain and is being investigated in addition to low-dose anticoagulation and aspirin. Other ongoing or planned studies will provide high-quality observational data on the role of transluminal angioplasty and stenting, submaximal balloon angioplasty alone, direct or indirect arterial bypass, and ischaemic conditioning for prevention of stroke in patients with ICAS.

Infarct Recurrence in Intracranial Atherosclerosis: Results from the MyRIAD Study.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is a common cause of ischemic stroke with a high risk of clinical stroke recurrence. Multiple mechanisms may underlie cerebral ischemia in this condition. The study's objective is to discern the mechanisms of recurrent ischemia in ICAD through imaging biomarkers of impaired antegrade flow, poor distal perfusion, abnormal vasoreactivity, and artery-to-artery embolism. METHODS: This prospective multicenter observational study enrolled patients with recent (≤21 days) ischemic stroke or transient ischemic attack (TIA) caused by ICAD with 50-99% stenosis treated medically. We obtained baseline quantitative MRA (QMRA), perfusion MRI (PWI), transcranial Doppler vasoreactivity (VMR), and emboli detection studies (EDS). The primary outcome was ischemic stroke in the territory of the stenotic artery within 1 year of follow-up; secondary outcomes were TIA at 1 year and new infarcts in the territory on MRI at 6-8 weeks. RESULTS: Amongst 102 of 105 participants with clinical follow-up (mean 253±131 days), the primary outcome occurred in 8.8% (12.7/100 patient-years), while 5.9% (8.5/100 patient-years) had a TIA. A new infarct in the territory of the symptomatic artery was noted in 24.7% at 6-8 weeks. A low flow state on QMRA was noted in 25.5%, poor distal perfusion on PWI in 43.5%, impaired vasoreactivity on VMR in 67.5%, and microemboli on EDS in 39.0%. No significant association was identified between these imaging biomarkers and primary or secondary outcomes. CONCLUSIONS: Despite intensive medical management in ICAD, there is a high risk of clinical cerebrovascular events at 1 year and an even higher risk of new imaging-evident infarcts in the subacute period after index stroke. Hemodynamic and plaque instability biomarkers did not identify a higher risk group. Further work is needed to identify mechanisms of ischemic stroke and infarct recurrence and their consequence on long-term physical and cognitive outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02121028.

Mitigating the effects of COVID-19 pandemic on controlling vascular risk factors among participants in a carotid stenosis trial.

INTRODUCTION: The COVID-19 pandemic has presented challenges to managing vascular risk factors with in-person follow-up of patients with asymptomatic carotid stenosis enrolled in the CREST2 trial. CREST2 is comparing intensive medical management alone versus intensive medical management plus revascularization with endarterectomy or stenting. We performed a study to evaluate the feasibility of a home-based program for testing blood pressure (BP) and low-density lipoprotein (LDL) in CREST2. METHODS: This study involved 45 patients at 10 sites in the CREST2 trial. The initial patients were identified by the Medical Management Core (MMC) as high-risk patients defined by stage 2 hypertension, LDL > 90 mg/dl, or both. If a patient at the site declined participation, another was substituted. All patients who agreed to participate were sent a BP monitoring device and a commercially available at-home lipid test kit that uses a self-performed finger-stick blood sample that was resulted to the patient. Training on the use of the equipment and obtaining the risk factor results was done by the study coordinator by telephone. RESULTS: Ten of the 130 currently active CREST2 sites participated, 8 in the LDL portion and 5 in the BP portion (3 sites did both). Twenty-six BP devices and 23 lipid tests were sent to patients. Of the 26 patients who obtained BP readings with the devices, 9 were out of the study target and adjustments in BP medications were made in 3. Of the 23 patients sent LDL tests, 13 were able to perform the test showing 7 were out of target, leading to adjustments in lipid medications in 4. CONCLUSION: This study established the feasibility of at-home monitoring of BP and LDL in a clinical trial and identified implementation challenges prior to widespread use in the trial. (ClinicalTrials.gov number NCT02089217).

Dual Antiplatelet Therapy Beyond 90 days in Symptomatic Intracranial Stenosis in the SAMMPRIS Trial.

BACKGROUND: The safety and efficacy of dual antiplatelet use for symptomatic intracranial atherosclerosis beyond 90 days is unknown. Data from SAMMPRIS was used to determine if dual antiplatelet therapy (DAPT) beyond 90 days impacted the risk of ischemic stroke and hemorrhage. METHODS: This post hoc exploratory analysis from SAMMPRIS included patients who did not have a primary endpoint within 90 days after enrollment (n = 397). Patients in both the aggressive medical management (AMM) and percutaneous transluminal angioplasty and stenting (PTAS) arms were included. Baseline features and outcomes during follow-up were compared between patients who remained on DAPT beyond 90 days (on clopidogrel) and patients who discontinued clopidogrel and remained on aspirin alone at 90 days (off clopidogrel) using Fisher's exact tests. RESULTS: The stroke rate was numerically lower in the group on clopidogrel vs off clopidogrel among both the AMM alone arm (6.0% versus 10.8%, p = 0.31) and the PTAS arm (8.7% versus 9.8%; p = 0.82), but the difference was not significant. The major hemorrhage rates were numerically higher in the group on clopidogrel vs. off clopidogrel group among both the AMM alone arm (4.0% versus 2.5%; p = 0.67) and the PTAS arm (10.9% versus 3.5%; p = 0.08), but were not significant. CONCLUSION: This exploratory analysis suggests that prolonged DAPT use may lower the risk of stroke in medically treated patients with intracranial stenosis but may increase the risk of major hemorrhage.

Mechanisms of early Recurrence in Intracranial Atherosclerotic Disease (MyRIAD): Rationale and design.

RATIONALE: Intracranial atherosclerotic disease (ICAD) is the most common cause of ischemic stroke with the highest rate of recurrence, despite aggressive medical management. Diverse mechanisms may be responsible for ICAD-related cerebral ischemia, with potential therapeutic implications. Here we present the rationale, design and methods of the Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease (MyRIAD) study. The aim of MyRIAD is to determine the mechanisms of stroke in ICAD through physiologic imaging biomarkers that evaluate impaired antegrade flow, poor distal perfusion, abnormal vasoreactivity, artery to artery embolism, and their interaction. METHODS AND DESIGN: This is a prospective observational study of patients with recently symptomatic (<21 days) ICAD with 50-99% stenosis treated medically and monitored for up to 1 year. An estimated 110 participants are recruited at 10 sites to identify the association between the presence of each mechanism of ischemia and recurrent stroke. The primary outcome is ischemic stroke in the territory of the symptomatic artery. Secondary outcomes include new cerebral infarction on MRI at 6-8 weeks and recurrent TIA in the territory of the symptomatic artery. DISCUSSION: MyRIAD is positioned to define the role of specific mechanisms of recurrent ischemia in patients with symptomatic ICAD. This knowledge will allow the development and implementation of effective and specific treatments for this condition.

Rationale, Design, and Implementation of Intensive Risk Factor Treatment in the CREST2 Trial.

BACKGROUND AND PURPOSE: The CREST2 trial (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis) is comparing intensive medical management (IMM) alone to IMM plus revascularization with carotid endarterectomy or transfemoral carotid artery stenting for preventing stroke or death within 44 days after randomization or ipsilateral ischemic stroke thereafter. There are extensive clinical trial data on outcomes after revascularization of asymptomatic carotid stenosis, but not for IMM. As such, the experimental treatment in CREST2 is IMM, which is described in this article. METHODS: IMM consists of aspirin 325 mg/day and intensive risk factor management, primarily targeting systolic blood pressure <130 mm Hg (initially systolic blood pressure <140 mm Hg) and LDL (low-density lipoprotein) cholesterol <70 mg/dL. Secondary risk factor targets focus on tobacco smoking, non-HDL (high-density lipoprotein), HbA1c (hemoglobin A1c), physical activity, and weight. Risk factor management is performed by site personnel and a lifestyle coaching program delivered by telephone. We report interim risk factor data on 1618 patients at baseline and last follow-up through 24 months. RESULTS: The mean baseline LDL of 80.5 mg/dL improved to 66.7 mg/dL. The mean baseline systolic blood pressure of 139.7 mm Hg improved to 130.3 mm Hg. The proportion of patients in-target improved from 43% to 61% for systolic blood pressure <130 mm Hg and from 45% to 67% for LDL<70 mg/dL (both changes P<0.001). CONCLUSIONS: The rigorous multimodal approach to intensive stroke risk factor management in CREST2 has resulted in significant improvements in risk factor control that will enable a comparison of cutting-edge medical care to revascularization in patients with asymptomatic carotid stenosis. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02089217.

New ischemic lesions on brain magnetic resonance imaging in patients with blunt traumatic cerebrovascular injury.

BACKGROUND: Patients with blunt cerebrovascular injuries are at risk of thromboembolic stroke. Although primary prevention with antithrombotic therapy is widely used in this setting, its effectiveness is not well defined and requires further investigation. The aim of this study was to evaluate the utility of magnetic resonance imaging (MRI)-detected ischemic brain lesions as a possible future outcome for randomized clinical trials in this patient population. METHODS: This prospective observational study included 20 adult blunt trauma patients admitted to a level I trauma center with a screening neck CTA showing extracranial carotid or vertebral artery injury. All subjects lacked initial evidence of an ischemic stroke and were managed with antithrombotic therapy and observation and then underwent brain MRI within 30 days of the injury to assess for ischemic lesions. The MRI scans included diffusion, susceptibility, and Fluid-attenuated Inversion Recovery (FLAIR) sequences, and were reviewed by two neuroradiologists blinded to the computed tomography angiography (CTA) findings. RESULTS: Eleven CTAs were done in the emergency department upon admission. There were 12 carotid artery dissections and 11 unilateral or bilateral vertebral artery injuries. Median interval between injury and MRI scan was 4 days (range, 0.1-14; interquartile range, 3-7 days). Diffusion-weighted imaging evidence of new ischemic lesions was present in 10 (43%) of 23 of the injured artery territories. In those injuries with ischemic lesions, the median number was 8 (range, 2-25; interquartile range, 5-8). None of the lesions were symptomatic. Blunt cerebrovascular injury was associated with a higher mean ischemic lesion count (mean count of 3.17 vs. 0.14, p < 0.0001), with the association remaining after adjusting for injury severity score (p < 0.0001). CONCLUSION: In asymptomatic blunt trauma patients with CTA evidence of extracranial cerebrovascular injury and treated with antithrombotic therapy, nearly half of arterial injuries are associated with ischemic lesions on MRI. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

Relationship Between Vascular Risk Factors and Location of Intracranial Atherosclerosis in the SAMMPRIS Trial.

BACKGROUND: Previous studies have reported that different locations of intracranial atherosclerosis (ICAS) are associated with different demographic features and vascular risk factors. We aimed to examine this observation in the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) trial population. METHODS: SAMMPRIS was a randomized controlled trial that enrolled 451 patients with recent transient ischemic attack or stroke-related due to severe (70%-99%) stenosis of a major intracranial artery. We compared the baseline demographic features and vascular risk factors between the symptomatic artery locations. Wilcoxon test was used to compare continuous variables, and chi-square test was used for categorical variables. RESULTS: Of 449 patients included in the analysis; 289 (64.4%) had ICAS in the anterior circulation and 160 (35.6%) in the posterior circulation. Features that were significantly different between patients with anterior versus posterior ICAS were: median age (58.3 years versus 64.0 years, P < .001), males/females (52.9%/47.1% versus 74.4%/25.6% P < .001), white/black (66.8%/26.6% versus 79.4%/16.9%, P = .02), and history of hyperlipidemia (85.5% versus 92.5%, P = .03). CONCLUSIONS: The observed differences in the distribution of demographic characteristics and vascular risk factors depending on the location of symptomatic ICAS suggest the possibility of different underlying pathological processes involved in the formation of atherosclerotic plaques in different locations.

Impact of Baseline Features and Risk Factor Control on Cognitive Function in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis Trial.

BACKGROUND: Cerebrovascular disease is an important cause of cognitive impairment. The aim of this study is to report the relationship between cognitive function and risk factors at baseline and during follow-up in the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) trial. METHODS: Subjects in the SAMMPRIS trial were included in this study. In order to have an assessment of cognitive function independent of stroke, patients with a stroke as a qualifying event whose deficits included aphasia or neglect were excluded from these analyses as were those with a cerebrovascular event during follow-up. The Montreal Cognitive Assessment (MoCA) score was used to assess cognitive impairment at baseline, 4 months, 12 months and closeout. Cognitive impairment was defined as MoCA < 26. A multivariate analysis was performed to determine what risk factors were independent predictors of cognitive function at baseline, 12 months and closeout. Among patients randomized to aggressive medical management only, the percentage of patients with cognitive impairment was compared between patients in versus out of target for each risk factor at 12 months and closeout. RESULTS: Of the 451 patients in SAMMPRIS, 371 patients met the inclusion criteria. MoCA < 26 was present in 55% at baseline. Older age and physical inactivity were associated with cognitive impairment at baseline. Older age, non-white race, lower baseline body mass index, and baseline cognitive impairment were associated with cognitive impairment at 12 months. In the aggressive medical management group, at 12 months, physical inactivity during follow-up was the strongest risk factor associated with cognitive impairment. CONCLUSION: Cognitive impairment is common in patients with severe symptomatic intracranial atherosclerosis. Physical inactivity at baseline and during follow-up is a strong predictor of cognitive impairment.

Hemodynamic Markers in the Anterior Circulation as Predictors of Recurrent Stroke in Patients With Intracranial Stenosis.

Background and Purpose- Although aggressive medical therapy was superior to stenting in the SAMMPRIS trial (Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis), the stroke rate in the medical arm was still high. The aim of this study was to determine the association between hemodynamic markers (borderzone infarct pattern and impaired collateral flow on baseline imaging) and rates of recurrent stroke in patients treated medically in SAMMPRIS. Methods- This was a post hoc analysis of patients whose qualifying event for SAMMPRIS was an infarct in the territory of a stenotic middle cerebral artery or intracranial carotid artery. Infarcts were adjudicated as involving primarily internal or cortical borderzone territories, the core middle cerebral artery territory, or perforator territories, and collateral flow was assessed according to a standard scale (American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology). Log-rank tests and χ2 tests were performed to assess associations of infarct patterns and collateral flow with rates of recurrent stroke. Results- Of 101 patients who qualified, 14 of 53 (26.4%) with borderzone infarcts, 2 of 24 (8.3%) with core middle cerebral artery infarcts, and 3 of 24 (12.5%) with perforator infarcts had a recurrent stroke in the territory (P=0.14 for comparing the 3 groups, P=0.052 for borderzone versus nonborderzone). Of 82 patients with collateral flow assessment, 30 of 43 (70%) with borderzone infarcts, 7 of 19 (37%) with core middle cerebral artery infarcts, and 11 of 20 (55%) with perforator infarcts had impaired collateral flow distal to the stenosis (P=0.049). Patients with borderzone infarcts and impaired collateral flow had the highest risk of recurrent stroke (37%). Conclusions- Borderzone infarcts and impaired collateral flow identify a subgroup of patients with intracranial stenosis who are at particularly high risk of recurrent stroke on medical treatment. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00576693.

Type and Duration of Exercise in the SAMMPRIS Trial.

BACKGROUND: Analyses from the Stenting and Aggressive Medical management for prevention of Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial showed that good control of vascular risk factors (systolic blood pressure, low-density lipoprotein, and exercise) was associated with fewer vascular events and exercise had the biggest impact on the outcome. We sought to determine the type and duration of exercise performed by SAMMPRIS patients during the trial. METHODS: SAMMPRIS aggressive medical management included a telephonic lifestyle modification program, INTERVENT, that was provided free of charge to all subjects during the study. We analyzed self-reported data collected by INTERVENT on the patients' type and duration of exercise from baseline (n=394) to 3 years (n=132). We calculated the mean duration for each exercise type at each time period and then compared the change in exercise duration from baseline using paired t tests and Wilcoxon signed-rank tests. RESULTS: Walking was the most common form of exercise at all time points, as measured by both the duration of exercise and the number of patients performing the exercise. The mean duration of walking and other aerobic activities increased significantly from baseline to all other time points. CONCLUSIONS: The type of self-reported exercise performed by SAMMPRIS patients included mostly walking or other aerobic activity and increased significantly during follow-up.

Relationship between Risk Factor Control and Compliance with a Lifestyle Modification Program in the Stenting Aggressive Medical Management for Prevention of Recurrent Stroke in Intracranial Stenosis Trial.

BACKGROUND: Lifestyle modification programs have improved the achievement of risk factor targets in a variety of clinical settings, including patients who have previously suffered a stroke or transient ischemic attack and those with multiple risk factors. Stenting Aggressive Medical Management for Prevention of Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) was the first vascular disease prevention trial to provide a commercially available lifestyle modification program to enhance risk factor control. We sought to determine the relationship between compliance with this program and risk factor control in SAMMPRIS. METHODS: SAMMPRIS aggressive medical management included a telephonic lifestyle modification program provided free of charge to all subjects (n = 451) during their participation in the study. Subjects with fewer than 3 expected lifestyle-coaching calls were excluded from these analyses. Compliant subjects (n = 201) had greater than or equal to 78.5% of calls (median % of completed/expected calls). Noncompliant subjects (n = 200) had less than 78.5% of calls or refused to participate. Mean risk factor values or % in-target for each risk factor was compared between compliant versus noncompliant subjects, using t tests and chi-square tests. Risk factor changes from baseline to follow-up were compared between the groups to account for baseline differences. RESULTS: Compliant subjects had better risk factor control throughout follow-up for low-density lipoprotein, systolic blood pressure (SBP), hemoglobin A1c (HgA1c), non-high-density lipoprotein, nonsmoking, and exercise than noncompliant subjects, but there was no difference for body mass index. After adjusting for baseline differences between the groups, compliant subjects had a greater change from baseline than noncompliant subjects for SBP did at 24 months and HgA1c at 6 months. CONCLUSION: SAMMPRIS subjects who were compliant with the lifestyle modification program had better risk factor control during the study for almost all risk factors.

Effects of Spaceflight on Astronaut Brain Structure as Indicated on MRI.

BACKGROUND: There is limited information regarding the effects of spaceflight on the anatomical configuration of the brain and on cerebrospinal fluid (CSF) spaces. METHODS: We used magnetic resonance imaging (MRI) to compare images of 18 astronauts' brains before and after missions of long duration, involving stays on the International Space Station, and of 16 astronauts' brains before and after missions of short duration, involving participation in the Space Shuttle Program. Images were interpreted by readers who were unaware of the flight duration. We also generated paired preflight and postflight MRI cine clips derived from high-resolution, three-dimensional imaging of 12 astronauts after long-duration flights and from 6 astronauts after short-duration flights in order to assess the extent of narrowing of CSF spaces and the displacement of brain structures. We also compared preflight ventricular volumes with postflight ventricular volumes by means of an automated analysis of T1-weighted MRIs. The main prespecified analyses focused on the change in the volume of the central sulcus, the change in the volume of CSF spaces at the vertex, and vertical displacement of the brain. RESULTS: Narrowing of the central sulcus occurred in 17 of 18 astronauts after long-duration flights (mean flight time, 164.8 days) and in 3 of 16 astronauts after short-duration flights (mean flight time, 13.6 days) (P<0.001). Cine clips from a subgroup of astronauts showed an upward shift of the brain after all long-duration flights (12 astronauts) but not after short-duration flights (6 astronauts) and narrowing of CSF spaces at the vertex after all long-duration flights (12 astronauts) and in 1 of 6 astronauts after short-duration flights. Three astronauts in the long-duration group had optic-disk edema, and all 3 had narrowing of the central sulcus. A cine clip was available for 1 of these 3 astronauts, and the cine clip showed upward shift of the brain. CONCLUSIONS: Narrowing of the central sulcus, upward shift of the brain, and narrowing of CSF spaces at the vertex occurred frequently and predominantly in astronauts after long-duration flights. Further investigation, including repeated postflight imaging conducted after some time on Earth, is required to determine the duration and clinical significance of these changes. (Funded by the National Aeronautics and Space Administration.).

Nonprocedural Symptomatic Infarction and In-Stent Restenosis After Intracranial Angioplasty and Stenting in the SAMMPRIS Trial (Stenting and Aggressive Medical Management for the Prevention of Recurrent Stroke in Intracranial Stenosis).

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the frequency of symptomatic in-stent restenosis (ISR) and its contribution to nonprocedural symptomatic infarction in the SAMMPRIS trial (Stenting and Aggressive Medical Management for the Prevention of Recurrent Stroke in Intracranial Stenosis). METHODS: Patients without a periprocedural primary end point were followed up to determine the occurrence of any of the following events: ischemic stroke, cerebral infarct with temporary signs, or transient ischemic attack in the territory of the stented artery. Vascular imaging performed after these events was reviewed for ISR. Annual rates for symptomatic ISR were calculated using Kaplan-Meier estimates. RESULTS: Of 183 patients in the stenting group without a periprocedural primary end point, 27 (14.8%) had a symptomatic infarction (stroke or cerebral infarct with temporary signs) and 16 (8.7%) had transient ischemic attack alone in the territory during a median follow-up of 35.0 months. Of the 27 patients with infarctions, 17 (9.3%) had an ischemic stroke and 10 (5.5%) had a cerebral infarct with temporary signs alone. Adequate vascular imaging to evaluate ISR was available in 24 patients with infarctions (showing ISR in 16 [66.7%]) and in 10 patients with transient ischemic attack alone (showing ISR in 8 [80%]). The 1-, 2-, and 3-year rates (with 95% confidence limits) for symptomatic ISR in the SAMMPRIS stent cohort were 9.6% (6.1%-14.9%), 11.3% (7.5%-17.0%), and 14.0% (9.6%-20.2%), respectively. CONCLUSIONS: Symptomatic ISR occurred in at least 1 of 7 patients in SAMMPRIS by 3 years of follow-up and was likely responsible for the majority of nonprocedural cerebral infarctions. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT00576693.

Stroke Caused by Atherosclerosis of the Major Intracranial Arteries.

Our goal in this review is to discuss the pathophysiology, diagnosis, and treatment of stroke caused by atherosclerosis of the major intracranial arteries. References for the review were identified by searching PubMed for related studies published from 1955 to June 2016 using search terms intracranial stenosis and intracranial atherosclerosis. Reference sections of published randomized clinical trials and previously published reviews were searched for additional references. Intracranial atherosclerotic disease is a highly prevalent cause of stroke that is associated with a high risk of recurrent stroke. It is more prevalent among blacks, Hispanics, and Asians compared with whites. Diabetes mellitus, hypertension, metabolic syndrome, smoking, hyperlipidemia, and a sedentary lifestyle are the major modifiable risk factors associated with intracranial atherosclerotic disease. Randomized clinical trials comparing aggressive management (dual antiplatelet treatment for 90 days followed by aspirin monotherapy and intensive management of vascular risk factors) with intracranial stenting plus aggressive medical management have shown medical management alone to be safer and more effective for preventing stroke. As such, aggressive medical management has become the standard of care for symptomatic patients with intracranial atherosclerotic disease. Nevertheless, there are subgroups of patients who are still at high risk of stroke despite being treated with aggressive medical management. Future research should aim to establish clinical, serological, and imaging biomarkers to identify high-risk patients, and clinical trials evaluating novel therapies should be focused on these patients.