Cameron G. McDougall

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.).

Pipeline for Uncoilable or Failed Aneurysms: Results from a Multicenter Clinical Trial

PURPOSE To evaluate the safety and effectiveness of the Pipeline Embolization Device (PED; ev3/Covidien, Irvine, Calif) in the treatment of complex intracranial aneurysms. MATERIALS AND METHODS The Pipeline for Uncoilable or Failed Aneurysms is a multicenter, prospective, interventional, single-arm trial of PED for the treatment of uncoilable or failed aneurysms of the internal carotid artery. Institutional review board approval of the HIPAA-compliant study protocol was obtained from each center. After providing informed consent, 108 patients with recently unruptured large and giant wide-necked aneurysms were enrolled in the study. The primary effectiveness endpoint was angiographic evaluation that demonstrated complete aneurysm occlusion and absence of major stenosis at 180 days. The primary safety endpoint was occurrence of major ipsilateral stroke or neurologic death at 180 days. RESULTS PED placement was technically successful in 107 of 108 patients (99.1%). Mean aneurysm size was 18.2 mm; 22 aneurysms (20.4%) were giant (>25 mm). Of the 106 aneurysms, 78 met the studys primary effectiveness endpoint (73.6%; 95% posterior probability interval: 64.4%-81.0%). Six of the 107 patients in the safety cohort experienced a major ipsilateral stroke or neurologic death (5.6%; 95% posterior probability interval: 2.6%-11.7%). CONCLUSION PED offers a reasonably safe and effective treatment of large or giant intracranial internal carotid artery aneurysms, demonstrated by high rates of complete aneurysm occlusion and low rates of adverse neurologic events; even in aneurysms failing previous alternative treatments.

Preliminary experience using the Neuroform stent for the treatment of cerebral aneurysms.

INTRODUCTIONThe Neuroform microstent—a flexible, self-expandable, microcatheter-delivered, nitinol stent designed for the treatment of cerebral aneurysms—was recently approved for use in patients. We present the results of our initial experience in using the Neuroform stent to treat patients with cerebral aneurysms, with an emphasis on potential applications, technical aspects of deployment, and associated intra- and periprocedural complications. METHODSThe records of all patients treated with the Neuroform stent were entered prospectively into a database. We assessed the clinical history, indications for stent use, aneurysm dimensions, and technical details of the procedures, including any difficulties with stent placement and/or deployment, degree of aneurysm occlusion, and complications. RESULTSDuring a 5-month period, 19 patients with 22 aneurysms were treated with the Neuroform stent. Twenty-five stents were deployed. Five patients had multiple stents placed. Five patients had ruptured aneurysms at the time of treatment. The indications for use were broad-necked aneurysms (n = 13; average neck length, 5.1 mm; average aneurysm size, 9 mm), fusiform or dissecting aneurysms (n = 3), salvage and/or bailout (n = 1), and giant aneurysms (n = 2). Technical problems included difficulty in deploying the stent (n = 6), inability to deploy the stent (n = 1), stent displacement (n = 2), inadvertent stent deployment (n = 1), and coil stretching (n = 1). Twenty-one of the 22 aneurysms were treated. Four aneurysms were stented without additional treatment, and 17 aneurysms were stented and coiled. Of the coiled aneurysms, complete or nearly complete (more than 95%) occlusion was achieved in 6 aneurysms, and partial occlusion was achieved in 11. Two clinically significant adverse events occurred, both of which were sequelae of periprocedural thromboembolic complications. One patient died after thrombolysis was attempted. The other patient made an excellent functional recovery after undergoing successful thrombolysis of a thrombosed basilar artery stent. CONCLUSIONThe Neuroform stent is a useful device for the treatment of patients with aneurysms that may not otherwise be amenable to endovascular therapy. In the majority of cases, the stent can be deployed accurately, even within the most tortuous segments of the cerebral vasculature. Although delivery and deployment may be technically challenging, clinically significant complications are uncommon.

The Barrow Ruptured Aneurysm Trial

OBJECT The purpose of this ongoing study is to compare the safety and efficacy of microsurgical clipping and endovascular coil embolization for the treatment of acutely ruptured cerebral aneurysms and to determine if one treatment is superior to the other by examining clinical and angiographic outcomes. The authors examined the null hypothesis that no difference exists between the 2 treatment modalities in the setting of subarachnoid hemorrhage (SAH). The current report is limited to the clinical results at 1 year after treatment. METHODS The authors screened 725 patients with SAH, resulting in 500 eligible patients who were enrolled prospectively in the study after giving their informed consent. Patients were assigned in an alternating fashion to surgical aneurysm clipping or endovascular coil therapy. Intake evaluations and outcome measurements were collected by nurse practitioners independent of the treating surgeons. Ultimately, 238 patients were assigned to aneurysm clipping and 233 to coil embolization. The 2 treatment groups were well matched. There were no anatomical exclusions. Crossing over was allowed, but primary outcome analysis was based on the initial treatment modality assignment. Posttreatment care was standardized for both groups. Patient outcomes at 1 year were independently assessed using the modified Rankin Scale (mRS). A poor outcome was defined as an mRS score > 2 at 1 year. The primary outcome was based on the assigned group; that is, by intent to treat. RESULTS One year after treatment, 403 patients were available for evaluation. Of these, 358 patients had actually undergone treatment. The remainder either died before treatment or had no identifiable source of SAH. A poor outcome (mRS score > 2) was observed in 33.7% of the patients assigned to aneurysm clipping and in 23.2% of the patients assigned to coil embolization (OR 1.68, 95% CI 1.08-2.61; p = 0.02). Of treated patients assigned to the coil group, 124 (62.3%) of the 199 who were eligible for any treatment actually received endovascular coil embolization. Patients who crossed over from coil to clip treatment fared worse than patients assigned to coil embolization, but no worse than patients assigned to clip occlusion. No patient treated by coil embolization suffered a recurrent hemorrhage. CONCLUSIONS One year after treatment, a policy of intent to treat favoring coil embolization resulted in fewer poor outcomes than clip occlusion. Although most aneurysms assigned to the coil treatment group were treated by coil embolization, a substantial number crossed over to surgical clipping. Although a policy of intent to treat favoring coil embolization resulted in fewer poor outcomes at 1 year, it remains important that high-quality surgical clipping be available as an alternative treatment modality.

Usefulness of the Neuroform stent for the treatment of cerebral aneurysms: results at initial (3-6-mo) follow-up.

OBJECTIVE: The Neuroform microstent, a flexible, self-expanding, nitinol stent specifically designed for use in the cerebral vasculature, became available in North America for aneurysm treatment in November 2002. The present report details our experience with the Neuroform stent over the past 2 years, with an emphasis on evolving treatment strategies and treatment durability at initial (3–6 mo) follow-up. METHODS: All patients included in this report were registered in a prospectively maintained database. We assessed the clinical history, indications for stent use, aneurysm dimensions, technical details of the procedures, degree of aneurysm occlusion, angiographic and clinical findings at follow-up, and complications. RESULTS: Over a 20-month period, 64 patients with 74 aneurysms were treated with 86 Neuroform stents. Of 64 patients, 16 (25%) were treated in the context of subarachnoid hemorrhage (8 acute, 7 subacute, 1 remote). Indications for stent use included broad aneurysm neck (n = 51 stents; average neck, 5.1 mm; aneurysm size, 8.2 mm), fusiform/dissecting morphology (n = 17), salvage/bailout for coils prolapsed into the parent vessel (n = 7), and giant aneurysm (n = 11). Sixty-one aneurysms were stented and coiled with complete or near complete (>95%) occlusion in 28 patients (45.9%) and partial occlusion (<95%) in 33 patients (54%). Follow-up angiographic (n = 43) or magnetic resonance angiographic (n = 5) data (average follow-up, 4.6 mo; median, 4 mo; range, 1.5–13 mo) for 48 aneurysms (46 patients) after stent-supported coil embolization demonstrated progressive thrombosis in 25 patients (52%), recanalization in 11 patients (23%) (8 of whom were retreated), and no change in 12 patients (25%). Follow-up angiography in 5 additional patients with dissecting aneurysms treated with stents alone demonstrated interval vascular remodeling with decreased aneurysm size in all patients. Delayed, severe, in-stent stenosis was observed in 3 patients, 1 of whom was symptomatic and required angioplasty and subsequently superficial temporal artery-to-middle cerebral artery bypass surgery. Using the second-generation Neuroform2 delivery system (n = 53), very few technical problems with stent delivery and deployment have been encountered (n = 2). CONCLUSION: The Neuroform stent facilitates adequate embolization of complex cerebral aneurysms, which would not otherwise be amenable to endovascular therapy. Initial follow-up data indicate favorable progressive thrombosis and recanalization rates for aneurysms after Neuroform stent-assisted embolization. These advantages of stenting were most evident for small aneurysms with wide necks.

US Multicenter Experience With the Wingspan Stent System for the Treatment of Intracranial Atheromatous Disease: Periprocedural Results

Background and Purpose— The current report details our initial periprocedural experience with Wingspan (Boston Scientific/Target), the first self-expanding stent system designed for the treatment of intracranial atheromatous disease. Methods— All patients undergoing angioplasty and stenting with the Gateway balloon–Wingspan stent system were prospectively tracked. Results— During a 9-month period, treatment with the stent system was attempted in 78 patients (average age, 63.6 years; 33 women) with 82 intracranial atheromatous lesions, of which 54 were ≥70% stenotic. Eighty-one of 82 lesions were successfully stented (98.8%) during the first treatment session. In 1 case, the stent could not be delivered across the lesion; the patient was treated solely with angioplasty and stented at a later date. Lesions treated involved the internal carotid (n=32; 8 petrous, 10 cavernous, 11 supraclinoid segment, 3 terminus), vertebral (n=14; V4 segment), basilar (n=14), and middle cerebral (n=22) arteries. Mean±SD pretreatment stenosis was 74.6±13.9%, improving to 43.5±18.1% after balloon angioplasty and to 27.2±16.7% after stent placement. Of the 82 lesions treated, there were 5 (6.1%) major periprocedural neurological complications, 4 of which ultimately led to patient death within 30 days of the procedure. Conclusions— Angioplasty and stenting for symptomatic intracranial atheromatous disease can be performed with the Gateway balloon–Wingspan stent system with a high rate of technical success and acceptable periprocedural morbidity. Our initial experience indicates that this procedure represents a viable treatment option for this patient population.

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.

Safety and efficacy of NA-1 in patients with iatrogenic stroke after endovascular aneurysm repair (ENACT): a phase 2, randomised, double-blind, placebo-controlled trial

BACKGROUND Neuroprotection with NA-1 (Tat-NR2B9c), an inhibitor of postsynaptic density-95 protein, has been shown in a primate model of stroke. We assessed whether NA-1 could reduce ischaemic brain damage in human beings. METHODS For this double-blind, randomised, controlled study, we enrolled patients aged 18 years or older who had a ruptured or unruptured intracranial aneurysm amenable to endovascular repair from 14 hospitals in Canada and the USA. We used a computer-generated randomisation sequence to allocate patients to receive an intravenous infusion of either NA-1 or saline control at the end of their endovascular procedure (1:1; stratified by site, age, and aneurysm status). Both patients and investigators were masked to treatment allocation. The primary outcome was safety and primary clinical outcomes were the number and volume of new ischaemic strokes defined by MRI at 12-95 h after infusion. We used a modified intention-to-treat (mITT) analysis. This trial is registered with ClinicalTrials.gov, number NCT00728182. FINDINGS Between Sept 16, 2008, and March 30, 2011, we randomly allocated 197 patients to treatment-12 individuals did not receive treatment because they were found to be ineligible after randomisation, so the mITT population consisted of 185 individuals, 92 in the NA-1 group and 93 in the placebo group. Two minor adverse events were adjudged to be associated with NA-1; no serious adverse events were attributable to NA-1. We recorded no difference between groups in the volume of lesions by either diffusion-weighted MRI (adjusted p value=0·120) or fluid-attenuated inversion recovery MRI (adjusted p value=0·236). Patients in the NA-1 group sustained fewer ischaemic infarcts than did patients in the placebo group, as gauged by diffusion-weighted MRI (adjusted incidence rate ratio 0·53, 95% CI 0·38-0·74) and fluid-attenuated inversion recovery MRI (0·59, 0·42-0·83). INTERPRETATION Our findings suggest that neuroprotection in human ischaemic stroke is possible and that it should be investigated in larger trials. FUNDING NoNO Inc and Arbor Vita Corp.

Wingspan in-stent restenosis and thrombosis: Incidence, clinical presentation, and management

OBJECTIVE: Wingspan (Boston Scientific, Fremont, CA) is a self-expanding stent designed specifically for the treatment of symptomatic intracranial atheromatous disease. The current series reports the observed incidence of in-stent restenosis (ISR) and thrombosis on angiographic follow-up. METHODS: A prospective, intent-to-treat registry of patients in whom the Wingspan stent system was used to treat symptomatic intracranial atheromatous disease was maintained at five participating institutions. Clinical and angiographic follow-up results were recorded. ISR was defined as stenosis greater than 50% within or immediately adjacent (within 5 mm) to the implanted stents and absolute luminal loss greater than 20%. RESULTS: To date, follow-up imaging (average duration, 5.9 mo; range, 1.5-15.5 mo) is available for 84 lesions treated with the Wingspan stent (78 patients). Follow-up examinations consisted of 65 conventional angiograms, 17 computed tomographic angiograms, and two magnetic resonance angiograms. Of these lesions with follow-up, ISR was documented in 25 and complete thrombosis in four. Two of the 4 patients with stent thrombosis had lengthy lesions requiring more than one stent to bridge the diseased segment. ISR was more frequent (odds ratio, 4.7; 95% confidence intervals, 1.4-15.5) within the anterior circulation (42%) than the posterior circulation (13%). Of the 29 patients with ISR or thrombosis, eight were symptomatic (four with stroke, four with transient ischemic attack) and 15 were retreated. Of the retreatments, four were complicated by clinically silent in-stent dissections, two of which required the placement of a second stent. One was complicated by a postprocedural reperfusion hemorrhage. CONCLUSION: The ISR rate with the Wingspan stent is higher in our series than previously reported, occurring in 29.7% of patients. ISR was more frequent within the anterior circulation than the posterior circulation. Although typically asymptomatic (76% of patients in our series), ISR can cause neurological symptoms and may require target vessel revascularization.OBJECTIVEWingspan (Boston Scientific, Fremont, CA) is a self-expanding stent designed specifically for the treatment of symptomatic intracranial atheromatous disease. The current series reports the observed incidence of in-stent restenosis (ISR) and thrombosis on angiographic follow-up. METHODSA prospective, intent-to-treat registry of patients in whom the Wingspan stent system was used to treat symptomatic intracranial atheromatous disease was maintained at five participating institutions. Clinical and angiographic follow-up results were recorded. ISR was defined as stenosis greater than 50% within or immediately adjacent (within 5 mm) to the implanted stents and absolute luminal loss greater than 20%. RESULTSTo date, follow-up imaging (average duration, 5.9 mo; range, 1.5–15.5 mo) is available for 84 lesions treated with the Wingspan stent (78 patients). Follow-up examinations consisted of 65 conventional angiograms, 17 computed tomographic angiograms, and two magnetic resonance angiograms. Of these lesions with follow-up, ISR was documented in 25 and complete thrombosis in four. Two of the 4 patients with stent thrombosis had lengthy lesions requiring more than one stent to bridge the diseased segment. ISR was more frequent (odds ratio, 4.7; 95% confidence intervals, 1.4–15.5) within the anterior circulation (42%) than the posterior circulation (13%). Of the 29 patients with ISR or thrombosis, eight were symptomatic (four with stroke, four with transient ischemic attack) and 15 were retreated. Of the retreatments, four were complicated by clinically silent in-stent dissections, two of which required the placement of a second stent. One was complicated by a postprocedural reperfusion hemorrhage. CONCLUSIONThe ISR rate with the Wingspan stent is higher in our series than previously reported, occurring in 29.7% of patients. ISR was more frequent within the anterior circulation than the posterior circulation. Although typically asymptomatic (76% of patients in our series), ISR can cause neurological symptoms and may require target vessel revascularization.

International Retrospective Study of the Pipeline Embolization Device: A Multicenter Aneurysm Treatment Study

BACKGROUND AND PURPOSE: Flow diverters are increasingly used in the endovascular treatment of intracranial aneurysms. Our aim was to determine neurologic complication rates following Pipeline Embolization Device placement for intracranial aneurysm treatment in a real-world setting. MATERIALS AND METHODS: We retrospectively evaluated all patients with intracranial aneurysms treated with the Pipeline Embolization Device between July 2008 and February 2013 in 17 centers worldwide. We defined 4 subgroups: internal carotid artery aneurysms of ≥10 mm, ICA aneurysms of <10 mm, other anterior circulation aneurysms, and posterior circulation aneurysms. Neurologic complications included spontaneous rupture, intracranial hemorrhage, ischemic stroke, permanent cranial neuropathy, and mortality. Comparisons were made with t tests or ANOVAs for continuous variables and the Pearson χ2 or Fisher exact test for categoric variables. RESULTS: In total, 793 patients with 906 aneurysms were included. The neurologic morbidity and mortality rate was 8.4% (67/793), highest in the posterior circulation group (16.4%, 9/55) and lowest in the ICA <10-mm group (4.8%, 14/294) (P = .01). The spontaneous rupture rate was 0.6% (5/793). The intracranial hemorrhage rate was 2.4% (19/793). Ischemic stroke rates were 4.7% (37/793), highest in patients with posterior circulation aneurysms (7.3%, 4/55) and lowest in the ICA <10-mm group (2.7%, 8/294) (P = .16). Neurologic mortality was 3.8% (30/793), highest in the posterior circulation group (10.9%, 6/55) and lowest in the anterior circulation ICA <10-mm group (1.4%, 4/294) (P < .01). CONCLUSIONS: Aneurysm treatment with the Pipeline Embolization Device is associated with the lowest complication rates when used to treat small ICA aneurysms. Procedure-related morbidity and mortality are higher in the treatment of posterior circulation and giant aneurysms.