David Fiorella

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.).

CURATIVE ENDOVASCULAR RECONSTRUCTION OF CEREBRAL ANEURYSMS WITH THE PIPELINE EMBOLIZATION DEVICE: THE BUENOS AIRES EXPERIENCE

OBJECTIVESThe Pipeline embolization device (PED) (Chestnut Medical Technologies, Inc., Menlo Park, CA) is a new microcatheter-delivered endovascular construct designed to achieve the curative reconstruction of the parent arteries giving rise to wide-necked and fusiform intracranial aneurysms. We present our initial periprocedural experience with the PED and midterm follow-up results for a series of 53 patients. METHODSPatients harboring large and giant wide-necked, nonsaccular, and recurrent intracranial aneurysms were selected for treatment. All patients were pretreated with dual antiplatelet medications for at least 72 hours before surgery and continued taking both agents for at least 6 months after treatment. A control digital subtraction angiogram was typically performed at 3, 6, and 12 months. RESULTSFifty-three patients (age range, 11–77 years; average age, 55.2 years; 48 female) with 63 intracranial aneurysms were treated with the PED. Small (n = 33), large (n = 22), and giant (n = 8) wide-necked aneurysms were included. A total of 72 PEDs were used. Treatment was achieved with a single PED in 44 aneurysms, with 2 overlapping PEDs in 17 aneurysms, and with 3 overlapping PEDs in 2 aneurysms. The mean time between the treatment and last follow-up digital subtraction angiogram was 5.9 months (range, 1–22 months). Complete angiographic occlusion was achieved in 56%, 93%, and 95% of aneurysms at 3 (n = 42), 6 (n = 28), and 12 (n = 18) months, respectively. The only aneurysm that remained patent at the time of the 12-month follow-up examination had been treated previously with stent-supported coiling. The presence of a preexisting endoluminal stent may have limited the efficacy of the PED reconstruction in this aneurysm. No aneurysms demonstrated a deterioration of angiographic occlusion during the follow-up period (i.e., no recanalizations). No major complications (stroke or death) were encountered during the study period. Three patients (5%), all with giant aneurysms, experienced transient exacerbations of preexisting cranial neuropathies and headache after the PED treatment. All 3 were treated with corticosteroids, and these symptoms resolved within 1 month. CONCLUSIONEndovascular reconstruction with the PED represents a safe, durable, and curative treatment of selected wide-necked, large and giant cerebral aneurysms. The rate of complete occlusion at the time of the 12-month follow-up examination approached 100% in the present study. To date, no angiographic recurrences have been observed during serial angiographic follow-up.

The Pipeline Embolization Device for the Intracranial Treatment of Aneurysms Trial

BACKGROUND AND PURPOSE: Endoluminal reconstruction with flow diverting devices represents a novel constructive technique for the treatment of cerebral aneurysms. We present the results of the first prospective multicenter trial of a flow-diverting construct for the treatment of intracranial aneurysms. MATERIALS AND METHODS: Patients with unruptured aneurysms that were wide-necked (>4 mm), had unfavorable dome/neck ratios (<1.5), or had failed previous therapy were enrolled in the PITA trial between January and May 2007 at 4 (3 European and 1 South American) centers. Aneurysms were treated with the PED with or without adjunctive coil embolization. All patients underwent clinical evaluation at 30 and 180 days and conventional angiography 180 days after treatment. Angiographic results were adjudicated by an experienced neuroradiologist at a nonparticipating site. RESULTS: Thirty-one patients with 31 intracranial aneurysms (6 men; 42–76 years of age; average age, 54.6 years) were treated during the study period. Twenty-eight aneurysms arose from the ICA (5 cavernous, 15 parophthalmic, 4 superior hypophyseal, and 4 posterior communicating segments), 1 from the MCA, 1 from the vertebral artery, and 1 from the vertebrobasilar junction. Mean aneurysm size was 11.5 mm, and mean neck size was 5.8 mm. Twelve (38.7%) aneurysms had failed (or recurred after) a previous endovascular treatment. PED placement was technically successful in 30 of 31 patients (96.8%). Most aneurysms were treated with either 1 (n = 18) or 2 (n = 11) PEDs. Fifteen aneurysms (48.4%) were treated with a PED alone, while 16 were treated with both PED and embolization coils. Two patients experienced major periprocedural stroke. Follow-up angiography demonstrated complete aneurysm occlusion in 28 (93.3%) of the 30 patients who underwent angiographic follow-up. No significant in-construct stenosis (≥50%) was identified at follow-up angiography. CONCLUSIONS: Intracranial aneurysm treatment with the PED is technically feasible and can be achieved with a safety profile analogous to that reported for stent-supported coil embolization. PED treatment elicited a very high rate (93%) of complete angiographic occlusion at 6 months in a population of the most challenging anatomic subtypes of cerebral aneurysms.

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.

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.

ADAPT FAST study: a direct aspiration first pass technique for acute stroke thrombectomy.

Background The development of new revascularization devices has improved recanalization rates and time, but not clinical outcomes. We report a prospectively collected clinical experience with a new technique utilizing a direct aspiration first pass technique with large bore aspiration catheter as the primary method for vessel recanalization. Methods 98 prospectively identified acute ischemic stroke patients with 100 occluded large cerebral vessels at six institutions were included in the study. The ADAPT technique was utilized in all patients. Procedural and clinical data were captured for analysis. Results The aspiration component of the ADAPT technique alone was successful in achieving Thrombolysis in Cerebral Infarction (TICI) 2b or 3 revascularization in 78% of cases. The additional use of stent retrievers improved the TICI 2b/3 revascularization rate to 95%. The average time from groin puncture to at least TICI 2b recanalization was 37 min. A 5MAX demonstrated similar success to a 5MAX ACE in achieving TICI 2b/3 revascularization alone (75% vs 82%, p=0.43). Patients presented with an admitting median National Institutes of Health Stroke Scale (NIHSS) score of 17.0 (12.0–21.0) and improved to a median NIHSS score at discharge of 7.3 (1.0–11.0). Ninety day functional outcomes were 40% (modified Rankin Scale (mRS) 0–2) and 20% (mRS 6). There were two procedural complications and no symptomatic intracerebral hemorrhages. Discussion The ADAPT technique is a fast, safe, simple, and effective method that has facilitated our approach to acute ischemic stroke thrombectomy by utilizing the latest generation of large bore aspiration catheters to achieve previously unparalleled angiographic outcomes.

Endovascular reconstruction with the Neuroform stent as monotherapy for the treatment of uncoilable intradural pseudoaneurysms.

OBJECTIVE:Intradural pseudoaneurysms have a malignant natural history and can be difficult to treat if parent vessel deconstruction is not feasible. These lesions often involve a long arterial segment and lack a defined saccular component that would safely accommodate the introduction of embolization coils. The current report describes the successful endovascular treatment of these lesions using a strategy of Neuroform stent reconstruction. METHODS:A retrospective review of the prospectively maintained Neuroform databases from our two institutions identified all intracranial aneurysms treated with the Neuroform stent alone, without embolization coils. The clinical charts, procedural data, and angiographic results were reviewed. RESULTS:Over a 38-month study period (10/02–2/06), 266 aneurysms were treated with the Neuroform stent. Of these, 10 were small “uncoilable” intradural pseudoaneurysms associated with subarachnoid hemorrhage. These lesions were treated using a strategy of endovascular stent reconstruction of the diseased vascular segment with one or more Neuroform stents (without concomitant coil embolization). Seven pseudoaneurysms were treated in the context of acute or subacute subarachnoid hemorrhage, and three were associated with a remote history of subarachnoid hemorrhage. Periprocedural complications occurred in two patients (clinically silent, intraprocedural thromboembolic event successfully treated with intra-arterial abciximab, symptomatic postprocedural stent thrombosis with successful thrombolysis, and excellent neurological recovery). Both complications occurred in patients with ruptured aneurysms and could be attributed to inadequate platelet inhibition at the time of the initial procedure. Follow-up conventional angiographic examinations were available for all 10 patients with pseudoaneurysms (1–18.5 mo; average, 9.0 mo). In nine cases, the aneurysms improved at follow-up, with either complete (n = 5) or near complete (n = 4) resolution. In one case, short-term follow-up (1 mo) demonstrated no significant change. No patient has rehemorrhaged after treatment. CONCLUSION:Endovascular Neuroform stent reconstruction represents an optimal strategy for the management of intradural pseudoaneurysms that require a constructive treatment strategy and are too small to accommodate the introduction of embolization coils. Nine out of 10 patients in the current series treated with this strategy demonstrated some degree of endovascular remodeling with either complete (n = 5) or partial (n = 4) angiographic resolution at follow-up. No rehemorrhages were encountered. Adequate antiplatelet therapy, even in the setting of acute subarachnoid hemorrhage, is prerequisite for the avoidance of thromboembolic complications.