ARISE I Consensus Statement on the Management of Chronic Subdural Hematoma.

ARISE (Aneurysm/AVM/cSDH Roundtable Discussion With Industry and Stroke Experts) organized a one-and-a-half day meeting and workshop and brought together representatives from academia, industry, and government to discuss the most promising approaches to improve outcomes for patients with chronic subdural hematoma (cSDH). The emerging role of middle meningeal artery embolization in clinical practice and the design of current and potential future trials were the primary focuses of discussion. Existing evidence for imaging, indications, agents, and techniques was reviewed, and areas of priority for study and key questions surrounding the development of new and existing treatments for cSDH were identified. Multiple randomized, controlled trials have met their primary efficacy end points, providing high-level evidence that middle meningeal artery embolization is a potent adjunctive therapy to the standard (surgical and nonsurgical) management of neurologically stable cSDH patients in terms of reducing rates of disease recurrence. Pooled data analyses following the formal conclusion and publication of these trials will form a robust foundation upon which guidelines can be strengthened for cSDH treatment modalities and optimal patient selection, as well as delineate future lines of investigation.

Aspiration thrombectomy versus stent retriever thrombectomy as first-line approach for large vessel occlusion (COMPASS): a multicentre, randomised, open label, blinded outcome, non-inferiority trial.

BACKGROUND: Stent retriever thrombectomy of large-vessel occlusion results in better outcomes than medical therapy alone. Alternative thrombectomy strategies, particularly a direct aspiration as first pass technique, while promising, have not been rigorously assessed for clinical efficacy in randomised trials. We designed COMPASS to assess whether patients treated with aspiration as first pass have non-inferior functional outcomes to those treated with a stent retriever as first line. METHODS: We did a multicentre, randomised, open label, blinded outcome, core lab adjudicated non-inferiority trial at 15 sites (ten hospitals and four specialty clinics in the USA and one hospital in Canada). Eligible participants were patients presenting with acute ischaemic stroke from anterior circulation large-vessel occlusion within 6 h of onset and an Alberta Stroke Program Early CT Score of greater than 6. We randomly assigned participants (1:1) via a central web-based system without stratification to either direct aspiration first pass or stent retriever first line thrombectomy. Those assessing primary outcomes via clinical examinations were masked to group assignment as they were not involved in the procedures. Physicians were allowed to use adjunctive technology as was consistent with their standard of care. The null hypothesis for this study was that patients treated with aspiration as first pass achieve inferior outcomes compared with those treated with a stent retriever first line approach. The primary outcome was non-inferiority of clinical functional outcome at 90 days as measured by the percentage of patients achieving a modified Rankin Scale score of 0-2, analysed by intent to treat; non-inferiority was established with a margin of 0·15. All randomly assigned patients were included in the safety analyses. This trial is registered at ClinicalTrials.gov, number: NCT02466893. FINDINGS: Between June 1, 2015, and July 5, 2017, we assigned 270 patients to treatment: 134 to aspiration first pass and 136 to stent retriever first line. A modified Rankin score of 0-2 at 90 days was achieved by 69 patients (52%; 95% CI 43·8-60·3) in the aspiration group and 67 patients (50%; 41·6-57·4) in the stent retriever group, showing that aspiration as first pass was non-inferior to stent retriever first line (pnon-inferiority=0·0014). Intracranial haemorrhage occurred in 48 (36%) of 134 in the aspiration first pass group, and 46 (34%) of 135 in the stent retriever first line group. All-cause mortality at 3 months occurred in 30 patients (22%) in both groups. INTERPRETATION: A direct aspiration as first pass thrombectomy conferred non-inferior functional outcome at 90 days compared with stent retriever first line thrombectomy. This study supports the use of direct aspiration as an alternative to stent retriever as first-line therapy for stroke thrombectomy. FUNDING: Penumbra.

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.

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.

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.

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.

Is There Benefit from Stenting on Cognitive Function in Intracranial Atherosclerosis?

BACKGROUND: Revascularization of stenotic cerebral arteries is hypothesized to improve cognition by increasing cerebral perfusion. AIMS: We compared cognition impairment among patients treated with percutaneous angioplasty and stenting (PTAS) and aggressive medical management (AMM) versus AMM alone in the Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis (SAMMPRIS) Trial. METHODS: In SAMMPRIS, 451 patients with recent transient ischemic attack or stroke attributed to 70-99% intracranial stenosis were randomized to PTAS plus AMM or AMM alone. Patients who had stroke as the qualifying event with National Institutes of Health Stroke Scale indicating aphasia or neglect were excluded from these analyses. Patients with a cerebrovascular event (ischemic stroke, cerebral infarct with temporary signs or intracranial hemorrhage) during follow-up were excluded from follow-up visit analyses. The Montreal Cognitive Assessment (MoCA) score was used to assess cognition impairment at baseline, 4 months, 12 months and closeout. Cognitive impairment was defined as MoCA <26. Mean MoCA scores and the percentage of patients with cognitive impairment were compared between treatment groups at each time point using t tests and chi-square tests. Differences in MoCA mean at baseline and follow-up time points were compared using mixed model repeated measures ANOVA and Tukey-Kramer tests. RESULTS: There were no significant differences between the treatment groups for mean MoCA at any time point. Mean MoCA scores improved in both groups. The percentage of patients with cognitive impairment in the AMM versus PTAS groups was not significantly different at any time point. CONCLUSIONS: Revascularization with PTAS showed no improvement in cognitive impairment over AMM alone among patients who did not have recurrent cerebrovascular events during follow-up.

Hemodynamics of Flow Diverters.

Cerebral aneurysms are pathological focal evaginations of the arterial wall at and around the junctions of the circle of Willis. Their tenuous walls predispose aneurysms to leak or rupture leading to hemorrhagic strokes with high morbidity and mortality rates. The endovascular treatment of cerebral aneurysms currently includes the implantation of fine-mesh stents, called flow diverters, within the parent artery bearing the aneurysm. By mitigating flow velocities within the aneurysmal sac, the devices preferentially induce thrombus formation in the aneurysm within hours to days. In response to the foreign implant, an endothelialized arterial layer covers the luminal surface of the device over a period of days to months. Organization of the intraneurysmal thrombus leads to resorption and shrinkage of the aneurysm wall and contents, eventually leading to beneficial remodeling of the pathological site to a near-physiological state. The devices' primary function of reducing flow activity within aneurysms is corollary to their mesh structure. Complete specification of the device mesh structure, or alternately device permeability, necessarily involves the quantification of two variables commonly used to characterize porous media-mesh porosity and mesh pore density. We evaluated the flow alteration induced by five commercial neurovascular devices of varying porosity and pore density (stents: Neuroform, Enterprise, and LVIS; flow diverters: Pipeline and FRED) in an idealized sidewall aneurysm model. As can be expected in such a model, all devices substantially reduced intraneurysmal kinetic energy as compared to the nonstented case with the coarse-mesh stents inducing a 65-80% reduction whereas the fine-mesh flow diverters induced a near-complete flow stagnation (∼98% reduction). We also note a trend toward greater device efficacy (lower intraneurysmal flow) with decreasing device porosity and increasing device pore density. Several such flow studies have been and are being conducted in idealized as well as patient-derived geometries with the overarching goals of improving device design, facilitating treatment planning (what is the optimal device for a specific aneurysm), and predicting treatment outcome (will a specific aneurysm treated with a specific device successfully occlude over the long term). While the results are generally encouraging, there is poor standardization of study variables between different research groups, and any consensus will only be reached after standardized studies are conducted on collectively large datasets. Biochemical variables may have to be incorporated into these studies to maximize predictive values.

Emergent carotid stenting and intra-arterial abciximab in acute ischemic stroke due to tandem occlusion.

OBJECTIVE: Acute occlusions of the extracranial internal carotid artery (ICA) and a major intracranial artery respond poorly to intravenous tissue plasminogen activator (tPA) and present an endovascular challenge. The aim of our study was to retrospectively delineate the feasibility of the combined use of emergent carotid stenting and intra-arterial (IA) Abciximab with intracranial revascularization in the setting of acute ischemic stroke and carotid occlusions at our institution. METHODS: Eleven patients with complete cervical carotid occlusion with or without concomitant intracranial ICA and/or MCA occlusion were identified from a single center, retrospective review of patients admitted to the Stroke unit. We evaluated all cases for complications of emergent cervical ICA recanalization employing carotid stenting and IA Abciximab. RESULTS: All patients had complete cervical carotid occlusion with (n = 8) or without (n = 3) concomitant intracranial ICA and/or MCA occlusion. Successful emergent cervical ICA recanalization was achieved in all cases. All patients were administered IA Abciximab (dose range 6-17 mg, average 11.4 mg) immediately following the cervical carotid stenting. There was complete recanalization in all patients with no procedural morbidity or mortality. A single case (1/11, 9%) developed asymptomatic hemorrhagic transformation. Upon discharge, 9 patients (9/11, 82%) had a mRS of 0-2 and 2 patients (2/11, 18%) had a mRS of 3. CONCLUSIONS: In acute ICA-MCA/distal ICA occlusions, extracranial stenting followed by intracranial IA Abciximab and thrombectomy appears feasible, effective, and safe. Further evaluation of this treatment strategy is warranted.

Impact of the New American Heart Association/American Stroke Association Definition of Stroke on the Results of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis Trial.

BACKGROUND: An American Heart Association/American Stroke Association (AHA/ASA) writing committee has recently recommended that tissue evidence of cerebral infarction associated with temporary symptoms (CITS) lasting <24 hours should be considered a stroke. We analyzed the impact of considering CITS as equivalent to stroke on the results of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial. METHODS: We compared outcomes in the medical (n = 227) and stenting (n = 224) groups in SAMMPRIS using the following primary end point (new components in bold): any stroke, CITS, or death within 30 days after enrollment or within 30 days after a revascularization procedure for the qualifying lesion during follow-up; or ischemic stroke or CITS in the territory of the qualifying artery beyond 30 days. We also compared the use of brain magnetic resonance imaging (MRI) after transient ischemic attacks (TIAs) in both treatment groups. RESULTS: By considering CITS as equivalent to stroke, the number of primary end points increased from 34 to 43 in the medical group and from 52 to 66 in the stenting group of SAMMPRIS. The Kaplan-Meier curves for the primary end points in the 2 groups were significantly different (P = .009). The percentage of patients with reported TIAs who underwent brain MRI was 69% in the medical group and 61% in the stenting group (P = .40). CONCLUSION: Using the AHA/ASA definition of stroke resulted in a substantially higher primary end point rate in both treatment groups and an even higher benefit from medical therapy over stenting than originally shown in SAMMPRIS. The higher rate of CITS in the stenting group was not due to ascertainment bias.

Acute Stroke Imaging Research Roadmap III Imaging Selection and Outcomes in Acute Stroke Reperfusion Clinical Trials: Consensus Recommendations and Further Research Priorities.

BACKGROUND AND PURPOSE: The Stroke Imaging Research (STIR) group, the Imaging Working Group of StrokeNet, the American Society of Neuroradiology, and the Foundation of the American Society of Neuroradiology sponsored an imaging session and workshop during the Stroke Treatment Academy Industry Roundtable (STAIR) IX on October 5 to 6, 2015 in Washington, DC. The purpose of this roadmap was to focus on the role of imaging in future research and clinical trials. METHODS: This forum brought together stroke neurologists, neuroradiologists, neuroimaging research scientists, members of the National Institute of Neurological Disorders and Stroke (NINDS), industry representatives, and members of the US Food and Drug Administration to discuss STIR priorities in the light of an unprecedented series of positive acute stroke endovascular therapy clinical trials. RESULTS: The imaging session summarized and compared the imaging components of the recent positive endovascular trials and proposed opportunities for pooled analyses. The imaging workshop developed consensus recommendations for optimal imaging methods for the acquisition and analysis of core, mismatch, and collaterals across multiple modalities, and also a standardized approach for measuring the final infarct volume in prospective clinical trials. CONCLUSIONS: Recent positive acute stroke endovascular clinical trials have demonstrated the added value of neurovascular imaging. The optimal imaging profile for endovascular treatment includes large vessel occlusion, smaller core, good collaterals, and large penumbra. However, equivalent definitions for the imaging profile parameters across modalities are needed, and a standardization effort is warranted, potentially leveraging the pooled data resulting from the recent positive endovascular trials.

Endovascular Treatment of a Complex Renal Artery Aneurysm Using Coils and the Pipeline Embolization Device in a Patient with a Solitary Kidney.

BACKGROUND: We report a case of endovascular treatment of a complex renal artery aneurysm using the Pipeline Embolization Device, a flow diverting stent which is indicated for the treatment of large and giant cerebral aneurysms. METHODS: A forty-year-old female with medically refractory hypertension and congenital agenesis of the right kidney was found to have a 2.8-cm left superior renal artery branch aneurysm. The patient was treated successfully using the Pipeline Embolization Device (Medtronic, Irvine, CA) with coil embolization of the aneurysm and of one outflow vessel. RESULTS: On 3-year follow-up, her renal function was normal, vascular imaging showed complete occlusion of the aneurysm, and physiological remodeling of the reconstructed artery and parenchymal imaging showed no evidence of renal infarction. CONCLUSION: Flow diverting stents are a valuable treatment option for visceral aneurysms with complex anatomy.

Do Patient Characteristics Explain the Differences in Outcome Between Medically Treated Patients in SAMMPRIS and WASID?

BACKGROUND AND PURPOSE: The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) medical group had a much lower primary end point rate than predicted from the preceding Warfarin Aspirin Symptomatic Intracranial Disease (WASID) trial. This result has been attributed to the aggressive medical therapy used in SAMMPRIS, but an alternative hypothesis is that SAMMPRIS patients were at lower risk. We undertook analyses to evaluate these competing hypotheses. METHODS: Using proportional hazards regression, we compared the SAMMPRIS primary end point between SAMMPRIS medical patients and WASID patients meeting the same qualifying criteria adjusted for confounding baseline characteristics. RESULTS: The unadjusted comparison of the SAMMPRIS primary end point showed a significantly higher risk for WASID patients (P=0.009, logrank test) with 12 month Kaplan-Meier estimates of 21.9% in WASID and 12.6% in SAMMPRIS and hazard ratio 1.9 (95% confidence interval =1.2-3.0). The analyses identified the following confounding factors that varied between the studies and that conferred a higher risk: lack of statin use at enrollment (hazard ratio =1.8, 95% confidence interval =1.1-2.9, P=0.027) that was more prevalent among WASID patients (39% versus 14%, P<0.0001) and prior infarcts in the territory of the symptomatic vessel (hazard ratio =1.8, 95% confidence interval =1.1-2.9, P=0.023) that was more prevalent among SAMMPRIS patients (34% versus 22%, P=0.015).The hazard ratio for WASID versus SAMMPRIS adjusted for these 2 characteristics was 1.9 (95% confidence interval =1.1-3.2). CONCLUSIONS: After adjustment for confounding baseline characteristics, WASID patients had an almost 2-fold higher risk of the SAMMPRIS primary end point, which supports the hypothesis that the lower rate of the primary end point in the medical arm of SAMMPRIS compared with WASID patients was as a result of the aggressive medical management used in SAMMPRIS. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00576693.

Does the Stenting Versus Aggressive Medical Therapy Trial Support Stenting for Subgroups With Intracranial Stenosis?

BACKGROUND AND PURPOSE: Although the Stenting Versus Aggressive Medical Therapy for Intracranial Arterial Stenosis (SAMMPRIS) trial showed that medical therapy alone was superior to stenting plus medical therapy for preventing recurrent strokes in patients with symptomatic intracranial stenosis, we determined whether SAMMPRIS supported the use of stenting in any subpopulations of patients with symptomatic intracranial arterial stenosis. METHODS: The primary outcome, 30-day stroke and death and later strokes in the territory of the qualifying artery, was compared in those with and without baseline factors in the 2 treatment arms, percutaneous transluminal angioplasty and stenting (PTAS) plus aggressive medical therapy versus aggressive medical therapy alone. Baseline factors included sex, age, race, diabetes mellitus, hypertension, lipid disorder, smoking status, type of qualifying event, qualifying event hypoperfusion symptoms, use of antithrombotic or proton pump inhibitor at baseline, days to enrollment, old infarcts in the same territory, percent stenosis, other artery stenosis, and location of the symptomatic artery. RESULTS: A total of 451 patients were enrolled, 227 randomized to aggressive medical therapy and 224 to PTAS. Of all variables evaluated, the observed 2-year event rates were higher with PTAS than with aggressive medical therapy in the vast majority and the interaction with treatment was not statistically significant for any of the factors. CONCLUSIONS: The SAMMPRIS results do not provide evidence to support the use of PTAS using the Wingspan stent system compared with medical treatment in any examined subpopulation of patients with symptomatic intracranial stenosis, including those with qualifying event hypoperfusion symptoms. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00576693.

Outcome in patients previously on antithrombotic therapy in the SAMMPRIS trial: subgroup analysis.

BACKGROUND AND PURPOSE: Stenting has been used as a rescue therapy in patients with intracranial arterial stenosis and a transient ischemic attack or stroke when on antithrombotic therapy (AT). We determined whether the stenting versus aggressive medical therapy for intracranial arterial stenosis (SAMMPRIS) trial supported this approach by comparing the treatments within subgroups of patients whose qualifying event (QE) occurred on versus off of AT. METHODS: The primary outcome, 30-day stroke and death and later strokes in the territory of the qualifying artery, was compared between (1) percutaneous transluminal angioplasty and stenting plus aggressive medical therapy (PTAS) versus aggressive medical management therapy alone (AMM) for patients whose QE occurred on versus off AT and between (2) patients whose QE occurred on versus off AT separately for the treatment groups. RESULTS: Among the 284/451 (63%) patients who had their QE on AT, the 2-year primary end point rates were 15.6% for those randomized to AMM (n=140) and 21.6% for PTAS (n=144; P=0.043, log-rank test). In the 167 patients not on AT, the 2-year primary end point rates were 11.6% for AMM (n=87) and 18.8% for PTAS (n=80; P=0.31, log-rank test). Within both treatment groups, there was no difference in the time to the primary end point between patients who were on or off AT (AMM, P=0.96; PTAS, P=0.52; log-rank test). CONCLUSIONS: SAMMPRIS results indicate that the benefit of AMM over PTAS is similar in patients on versus off AT at the QE and that failure of AT is not a predictor of increased risk of a primary end point. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00576693.

Aggressive medical treatment with or without stenting in high-risk patients with intracranial artery stenosis (SAMMPRIS): the final results of a randomised trial.

BACKGROUND: Early results of the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis trial showed that, by 30 days, 33 (14·7%) of 224 patients in the stenting group and 13 (5·8%) of 227 patients in the medical group had died or had a stroke (percentages are product limit estimates), but provided insufficient data to establish whether stenting offered any longer-term benefit. Here we report the long-term outcome of patients in this trial. METHODS: We randomly assigned (1:1, stratified by centre with randomly permuted block sizes) 451 patients with recent transient ischaemic attack or stroke related to 70-99% stenosis of a major intracranial artery to aggressive medical management (antiplatelet therapy, intensive management of vascular risk factors, and a lifestyle-modification programme) or aggressive medical management plus stenting with the Wingspan stent. The primary endpoint was any of the following: stroke or death within 30 days after enrolment, ischaemic stroke in the territory of the qualifying artery beyond 30 days of enrolment, or stroke or death within 30 days after a revascularisation procedure of the qualifying lesion during follow-up. Primary endpoint analysis of between-group differences with log-rank test was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT 00576693. FINDINGS: During a median follow-up of 32·4 months, 34 (15%) of 227 patients in the medical group and 52 (23%) of 224 patients in the stenting group had a primary endpoint event. The cumulative probability of the primary endpoints was smaller in the medical group versus the percutaneous transluminal angioplasty and stenting (PTAS) group (p=0·0252). Beyond 30 days, 21 (10%) of 210 patients in the medical group and 19 (10%) of 191 patients in the stenting group had a primary endpoint. The absolute differences in the primary endpoint rates between the two groups were 7·1% at year 1 (95% CI 0·2 to 13·8%; p=0·0428), 6·5% at year 2 (-0·5 to 13·5%; p=0·07) and 9·0% at year 3 (1·5 to 16·5%; p=0·0193). The occurrence of the following adverse events was higher in the PTAS group than in the medical group: any stroke (59 [26%] of 224 patients vs 42 [19%] of 227 patients; p=0·0468) and major haemorrhage (29 [13%]of 224 patients vs 10 [4%] of 227 patients; p=0·0009). INTERPRETATION: The early benefit of aggressive medical management over stenting with the Wingspan stent for high-risk patients with intracranial stenosis persists over extended follow-up. Our findings lend support to the use of aggressive medical management rather than PTAS with the Wingspan system in high-risk patients with atherosclerotic intracranial arterial stenosis. FUNDING: National Institute of Neurological Disorders and Stroke (NINDS) and others.

Stenting versus aggressive medical therapy for intracranial arterial stenosis.

BACKGROUND: Atherosclerotic intracranial arterial stenosis is an important cause of stroke that is increasingly being treated with percutaneous transluminal angioplasty and stenting (PTAS) to prevent recurrent stroke. However, PTAS has not been compared with medical management in a randomized trial. METHODS: We randomly assigned patients who had a recent transient ischemic attack or stroke attributed to stenosis of 70 to 99% of the diameter of a major intracranial artery to aggressive medical management alone or aggressive medical management plus PTAS with the use of the Wingspan stent system. The primary end point was stroke or death within 30 days after enrollment or after a revascularization procedure for the qualifying lesion during the follow-up period or stroke in the territory of the qualifying artery beyond 30 days. RESULTS: Enrollment was stopped after 451 patients underwent randomization, because the 30-day rate of stroke or death was 14.7% in the PTAS group (nonfatal stroke, 12.5%; fatal stroke, 2.2%) and 5.8% in the medical-management group (nonfatal stroke, 5.3%; non-stroke-related death, 0.4%) (P=0.002). Beyond 30 days, stroke in the same territory occurred in 13 patients in each group. Currently, the mean duration of follow-up, which is ongoing, is 11.9 months. The probability of the occurrence of a primary end-point event over time differed significantly between the two treatment groups (P=0.009), with 1-year rates of the primary end point of 20.0% in the PTAS group and 12.2% in the medical-management group. CONCLUSIONS: In patients with intracranial arterial stenosis, aggressive medical management was superior to PTAS with the use of the Wingspan stent system, both because the risk of early stroke after PTAS was high and because the risk of stroke with aggressive medical therapy alone was lower than expected. (Funded by the National Institute of Neurological Disorders and Stroke and others; SAMMPRIS ClinicalTrials.gov number, NCT00576693.).

Intracranial stenosis: impact of randomized trials on treatment preferences of US neurologists and neurointerventionists.

BACKGROUND AND PURPOSE: Medical and endovascular treatment options for stroke prevention in patients with symptomatic intracranial stenosis have evolved over the past several decades, but the impact of 2 major multicenter randomized stroke prevention trials on physician practices has not been studied. We sought to determine changes in US physician treatment choices for patients with intracranial atherosclerotic stenosis (ICAS) following 2 NIH-funded clinical trials that studied medical therapies (antithrombotic agents and risk factor control) and percutaneous transluminal angioplasty and stenting (PTAS). METHODS: Anonymous surveys on treatment practices in patients with ICAS were sent to physicians at 3 time points: before publication of the NIH-funded Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial (pre-WASID survey, 2004), 1 year after WASID publication (post-WASID survey, 2006) and 1 year after the publication of the NIH-funded Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial (post-SAMMPRIS survey, 2012). Neurologists were invited to participate in the pre-WASID survey (n=525). Neurologists and neurointerventionists were invited to participate in the post-WASID (n=598) and post-SAMMPRIS (n=2,080) surveys. The 3 surveys were conducted using web-based survey tools delivered by E-mail, and a fax-based response form delivered by E-mail and conventional mail. Data were analyzed using the χ2 test. RESULTS: Before WASID, there was equipoise between warfarin and aspirin for stroke prevention in patients with ICAS. The number of respondents who recommended antiplatelet treatment for ICAS increased across all 3 surveys for both anterior circulation (pre-WASID=44%, post-WASID=85%, post-SAMMPRIS=94%) and posterior circulation (pre-WASID=36%, post-WASID=74%, post-SAMMPRIS=83%). The antiplatelet agent most commonly recommended after WASID was aspirin, but after SAMMPRIS it was the combination of aspirin and clopidogrel. The percentage of neurologists who recommended PTAS in >25% of ICAS patients increased slightly from pre-WASID (8%) to post-WASID surveys (12%), but then decreased again after SAMMPRIS (6%). The percentage of neurointerventionists who recommended PTAS in >25% of ICAS patients decreased from post-WASID (49%) to post-SAMMPRIS surveys (17%). CONCLUSIONS: The surveyed US physicians' recommended treatments for ICAS differed over the 3 survey periods, reflecting the results of the 2 NIH-funded clinical trials of ICAS and suggesting that these clinical trials changed practice in the USA.

First-in-man experience with the ReVive PV peripheral thrombectomy device for the revascularization of below-the-knee embolic occlusions.

PURPOSE: To report the initial use of a novel thrombectomy device for revascularization of below-the-knee thromboembolic occlusions encountered during proximal revascularization procedures. CASE REPORTS: The ReVive PV Peripheral Thrombectomy Device is a non-detachable, self-expanding stent-like device recently approved for peripheral thrombectomy. Four patients (3 women; mean age 68.8 years) undergoing proximal revascularization procedures experienced embolic occlusions of all 3 trifurcation vessels in 1 patient, the tibioperoneal trunk alone in 2 cases, and the peroneal artery alone in the last patient. In all cases, the involved arteries represented the primary or sole vessel(s) providing outflow to the lower extremity. In each case, the ReVive PV device was used to successfully extract the thrombus and restore flow to the distal extremity. No complications were encountered during any of the procedures. CONCLUSION: The ReVive PV peripheral thrombectomy device may facilitate the safe and efficient revascularization of distal arterial embolic occlusions.