Stenting And Aggressive Medical Management For Preventing Recurrent Stroke In Intracranial Stenosis Research Articles

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.

Abstract WMP47: Poor Risk Factor Control and Lower Levels of Physical Activity Predict Incident Major Cardiovascular Events in Patients With Symptomatic Vertebrobasilar Disease: A Post-Hoc Analysis of the SAMMPRIS Trial

Background: Symptomatic vertebrobasilar (VB) atherosclerotic disease is associated with a high risk of recurrent stroke despite optimal medical therapy. Objective: In this study, we aim to examine the prognosis and associations between risk factors and recurrent major cardiovascular events (MACE) in patients with symptomatic VB stenosis randomized in the medical arm of the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study. Methods: Data from subjects in the medical arm of the SAMMPRIS trial with an infarct in the territory of vertebral or basilar arteries (n= 73) were analyzed. The primary outcome was MACE: defined as stroke, myocardial infarction, or other cardiovascular death during follow up. Mean risk factor values were compared between subjects who met the primary outcome at 2 years versus those who did not, using T-tests and χ2 tests. Results: Among 73 patients with VB stenosis randomized to medical treatment, 18 patients (24.6%) had recurrent MACE over a mean follow up of 2.8 years. This was significantly less than the rate of MACE in those with VB enrolled in the WASID trial (9.7 per 100-patient years vs. 20.9 per 100-patient years, p&lt;0.01). Predictors of MACE at 2 years were increased triglyceride level (adjusted OR per 50 units increase in triglyceride 1.94, 95% CI 1.15-3.28) and increased HbA1c level (adjusted OR per 1 unit increase in HbA1c 2.07, 95% CI 0.97-4.45), and lower physical activity status measured by PACE (out of target defined by PACE ≤ 4: moderate activity &lt; 5 days per week or intense activity &lt; 3 days per week) (2.5 ± 1.0 vs. 3.3 ± 1.8, p = 0.028) (Table). Conclusions: In patients with symptomatic VB disease, improvement of medical treatment over time led to a reduction in cardiovascular event rates but this risk remains elevated as nearly 1 in 5 patients had MACE within 2 years. Further risk factor optimization and lifestyle changes are needed to reduce the rates of MACE in this patient population.

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.

Percutaneous Transluminal Angioplasty with Stent Placement versus Best Medical Therapy Alone in Symptomatic Intracranial Arterial Stenosis: A Best Evidence Review.

Intracranial arterial stenosis (ICAS) is a common cause of stroke, and the risk of ischemic stroke from a stenotic intracranial artery remains high despite best medical therapy (BMT). As a result, clinicians have increasingly turned to percutaneous transluminal angioplasty and stenting (PTAS) over the last decade as an alternative therapy in high-risk patients with symptomatic ICAS. In this review, we will critically analyze multiple clinical trials to assess the safety and efficacy of PTAS with BMT versus BMT alone. The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial reported a higher rate of stroke or death within 30 days in the PTAS plus BMT group (14.7%) than the BMT only group (5.8%, p = 0.002). The rate of any stroke during the follow-up period (mean = 32 months) was higher in the PTAS plus BMT group (22.3%) than the BMT only group (14.1%, p = 0.03). The Vitesse Intracranial Stent Study for Ischemic Stroke Therapy (VISSIT) trial reported a higher rate of stroke or death within 30 days in the PTAS plus BMT cohort (24.1%) than the BMT only cohort (9.4%, p = 0.05). There was also a higher rate of hard transient ischemic attack (TIA) or stroke within one year in the PTAS plus BMT group (36.2%) than the BMT only group (15.1%, p = 0.02). The Vertebral Artery Ischaemia Stenting (VIST) trial reported the rate of any stroke during the follow-up period to be two events in 50 person-years in the PTAS plus BMT cohort versus four events in 45 person-years in the BMT only cohort, with a calculated hazard ratio of 0.47 (p = 0.39). Vertebral Artery Stenting Trial (VAST) reported a higher incidence of stroke, MI, or vascular death in the PTAS with BMT cohort (22%) than the BMT only cohort (0%). Tang et al. reported no significant difference in the incidence of vascular events at one year and three years between the PTAS plus BMT and BMT only cohorts. However, the distribution of vascular events was more concentrated in the first postoperative week in the PTAS plus BMT cohort (75% of all vascular events) versus the BMT only cohort (17%). Feng et al. reported a lower periprocedural complication rate (9.1%) with the Enterprise stent in comparison to the Wingspan and balloon-expandable stents used in the SAMMPRIS and VISSIT trials. We conclude that PTAS should not be employed as first-line treatment in patients with symptomatic ICAS. However, PTAS should be considered in symptomatic ICAS patients that are hemodynamically unstable or have repeatedly failed BMT, especially at sites with lower rates of perioperative complications than those reported here.

Abstract TP203: The Effect of Concurrent Presence of Atherosclerotic Disease in Other Arterial Distributions in Patients With Symptomatic Intracranial Stenosis

Objective: To determine the effect of concurrent presence of atherosclerotic disease in other arterial distributions (ADOAD) on risk of 30 day stroke or death and ischemic stroke in the territory of the symptomatic intracranial artery beyond 30 days after enrollment in patients with severe (70-99%) intracranial stenosis recruited in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) Trial. Methods: Patients with known history of myocardial infarction, angina, carotid endarterectomy, coronary artery bypass surgery, previous angioplasty and stenting, or peripheral arterial disease at baseline evaluation were classified as those with concurrent presence of ADOAD. Hazards ratio (HR) for primary event during follow up was estimated using Cox proportional hazards analysis after adjusting for age, gender, location of stenosis, and treatment allocated (stent placement versus best medical treatment). Results: A total of 126 of 451 patients included had concurrent presence of ADOAD. After adjusting for potential confounders, the risk of primary endpoint was not significantly different in patients with concurrent presence of ADOAD (HR 1.14, 95% confidence interval [CI] 0.7 - 1.9). The treatment effect of stent placement (compared with best medical treatment) was not different in patients with concurrent presence of ADOAD (HR of 0.9 and 1.1, respectively) after adjusting for potential cofounders. The risk of any ischemic stroke (HR 1.3, 95% CI 0.8 - 2.3) and death (HR 1.4, 95% CI 0.3 - 7.1) during follow up was not different with concurrent presence of ADOAD. Conclusions: There was no effect on cardiovascular endpoints in patients with high grade symptomatic intracranial stenosis and concurrent presence of ADOAD from both natural history and treatment perspective.

Abstract TP426: Major Cognitive Improvement in Patients With High Grade Intracranial Stenosis (70-99%) Within 3 Months of Transient Ischemic Attack or Minor Ischemic Stroke

Importance: Cognitive impairment appears to be common manifestation in patients with high grade intracranial stenosis. The rates of improvement in cognitive impairment and associated factors are not well known. Objective: Identify the rates and predictors of major cognitive improvement in patients with non-disabling stroke or TIA attributed to 70%-99% stenosis of a major intracranial artery. Methods: A post hoc analysis of patients in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) Trial was performed. Each patient underwent cognitive assessment using the Montreal Cognitive Assessment (MoCA) prior to (within 30 day of TIA or non-disabling stroke) and at 3 months post randomization. Major cognitive improvement was defined by an increase in Montreal Cognitive Assessment score of 2 points or greater at follow up evaluation. Results: A total of 172 (38.1%, 95% confidence interval [CI] 32.8 - 44.2) of 451 patients randomized had major improvement in cognitive assessment. The rate of major cognitive improvement was 151 (33.5% 95% CI 28.5 - 39.2) and 21 (4.7% 95% CI 3.0 - 7.0) among patients with MoCA score of &lt;26 and ≥26 at baseline evaluation. The rates of major cognitive improvement did not differ between patients who were randomized to stent placement compared with best medical treatment (85 [49.4%] versus 87 [50.6%], relative risk [RR] 1.1, p=0.4). The rates of major cognitive improvement were significantly higher among patients aged ≥65 years (72 [41.9%] versus 55 [31.1%], relative risk [RR] 0.8, p=.03) and those with systolic BP ≥140 mm Hg at follow up visit (53 [30.8%] versus 39 (22.0%), relative risk [RR] 0.9, p=.05). There was a trend towards lower rates of major cognitive improvement in patients with HbA1C &gt;6 at baseline assessment. No relationship between LDL cholesterol ≥70 mg/dl at baseline or follow up visit and major cognitive improvement was identified. Conclusions: A relatively high rate of major cognitive improvement was observed in patients with high grade symptomatic intracranial stenosis within 3 months. The paradoxical relationship between greater age and higher systolic blood pressure at follow up evaluation with major cognitive improvement require further studies.

Concomitant Asymptomatic Intracranial Atherosclerotic Stenosis Increase the 30-Day Risk of Stroke in Patients Undergoing Symptomatic Intracranial Atherosclerotic Stenosis Stenting

In the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial, 19.1% of ischemic strokes occurred out of the territory of previously symptomatic stenosis during the mean follow-up period of 23.4 months. However, it is unknown how many ischemic strokes were due to a previously asymptomatic intracranial atherosclerotic stenosis (ICAS). The objective of this study was to investigate whether the concomitant asymptomatic ICAS influences the outcome of patients undergoing symptomatic ICAS stenting. We retrospectively reviewed 576 consecutive patients with nondisabling ischemic stroke (modified Rankin scale score of ≤3) who were treated with symptomatic ICAS (≥70% stenosis) stenting with or without concomitant asymptomatic ICAS. The baseline characteristics and the 30-day primary end points (stroke or death after stenting) were compared by bivariate and multivariable logistic analyses. The 30-day rate of primary end points was 5.2%, which was higher in patients with concomitant asymptomatic ICAS (≥50% stenosis) than in those without asymptomatic ICAS (no stenosis or <50% stenosis) (8.9% versus 3.8%, P = .014). In patients with concomitant asymptomatic ICAS, 25% of ischemic strokes occurred out of the territory of the stented artery, whereas in patients without asymptomatic ICAS, no ischemic stroke occurred out of the territory of the stented artery. Multivariable analysis showed that concomitant asymptomatic ICAS was an independent risk factor for 30-day stroke (odds ratio = 2.37, 95% confidence interval, 1.14-5.63; P = .023). Concomitant asymptomatic ICAS (≥50% stenosis) might increase the 30-day risk of stroke in patients undergoing symptomatic ICAS stenting.

Medical Treatment of Intracranial Atherosclerosis: An Update.

For patients with symptomatic intracranial atherosclerosis (ICAS), antithrombotic agents are the mainstay of therapy. Anticoagulation (warfarin) is not widely used since it is not more effective than aspirin and carries a high risk of bleeding. New oral anticoagulants are showing promise, but their use has not been investigated in appropriate clinical trials. Since the recurrent stroke risk is high with aspirin monotherapy, dual antiplatelets are considered in the early stage of symptomatic ICAS. Based on the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) and Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) results, aspirin plus clopidogrel has been recommended. However, this combination was not superior to aspirin monotherapy in patients with ICAS in the CHANCE substudy. Progression of ICAS is common, and it is associated with recurrent strokes. In the Trial of Cilostazol in Symptomatic Intracranial Arterial Stenosis (TOSS) study, aspirin plus cilostazol was more effective than aspirin monotherapy in preventing progression. The TOSS II trial showed that the overall change in stenosis was better with aspirin plus cilostazol than with aspirin plus clopidogrel. Aside from antithrombotic therapy, risk factor management is critical for secondary prevention, and high blood pressure is clearly linked to recurrent stroke. However, blood pressure may have to be cautiously managed in the early stage of stroke. Considering that ICAS is the major cause of stroke worldwide, further investigations are needed to establish optimal management strategies for patients with ICAS.

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

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. 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. 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). 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.

Management of Symptomatic Intracranial Stenosis.

Intracranial atherosclerotic disease is a common cause of stroke worldwide, causing approximately 10% of strokes in the USA and up to 50% in Asian populations. Recurrent stroke risks are particularly high in those with a stenosis of 70% or more and a recent transient ischemic attack or stroke. Warfarin has been associated with higher major hemorrhage rates and no reduction of recurrent stroke compared to aspirin in patients with symptomatic intracranial stenosis. After early trials showed the feasibility of stenting, two randomized trials compared stenting plus medical management to medical management alone in symptomatic intracranial stenosis. Stenting was linked with increased risk and showed no benefit in any subpopulation of patients. Aggressive medical management in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial was associated with half the risk of stroke compared to that in similar patients in a previous symptomatic intracranial stenosis trial after adjustment of confounding characteristics. Aggressive medical management comprises risk factor control, including a target systolic blood pressure <140mmHg, a low density lipoprotein <70mg/dL, hemoglobin A1C <7.0%, and lifestyle management that incorporates exercise, smoking cessation and weight management, and the use of antithrombotics.

Clopidogrel plus Aspirin for Symptomatic Intracranial Atherosclerotic Stenosis: A Pilot Study

Background and Purpose: There are limited data on the optimal duration of dual antiplatelet therapy for secondary stroke prevention in patients with symptomatic intracranial atherosclerotic disease. Methods: Consecutive patients presenting with high-grade (70-99%) symptomatic intracranial stenosis from January 1, 2011, to December 31, 2013, and evaluated within 30 days of the index event were eligible for this analysis. All patients underwent treatment with aspirin plus clopidogrel for a target duration of 12 months along with aggressive medical management based on the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) protocol; all patients were given gastrointestinal prophylaxis for the duration of their aspirin and clopidogrel treatment. Clinical and safety outcomes of our cohort were compared with the medical arm of the SAMMPRIS trial cohort (n = 227). Results: Our cohort included 25 patients that met the inclusion criteria. Achievement of blood pressure and LDL cholesterol targets were similar between our cohort and the SAMMPRIS cohort. At 1 year, the rates of stroke, myocardial infarction or vascular death were 0% in our cohort and 16% in the SAMMPRIS cohort (p = 0.03). At 1 year, major bleeding rates were similar between our cohort and the SAMMPRIS cohort (4 vs. 2.2%, p = 1.0). Conclusion: A prolonged course of dual antiplatelet therapy for symptomatic intracranial atherosclerotic disease may be associated with less vascular events with no increase in hemorrhagic complications.

Factors Associated With Recurrent Ischemic Stroke in the Medical Group of the SAMMPRIS Trial.

The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) Trial showed that aggressive medical therapy was more effective than stenting for preventing stroke in patients with symptomatic intracranial stenosis. However, 15% of patients in the medical group still experienced a primary end point during a median follow-up of 32.7 months. To determine baseline features that were associated with a high rate of a primary end point in the medical arm of the SAMMPRIS Trial. A post hoc analysis of patients in the medical arm only of the SAMMPRIS trial. Enrollment occurred between October 2008 and April 2013 and included 227 patients randomized to medical management alone. Baseline demographic features, vascular risk factors, qualifying event, brain imaging, and angiographic features were analyzed. Bivariate and multivariable proportional hazard regression modeling was performed to relate baseline features to the time until a primary end point. The post hoc analysis was conducted from November 2014 to June 2015. The SAMMPRIS Trial compared stenting with aggressive medical management in patients with a stroke or transient ischemic attack attributed to 70% to 99% stenosis of a major intracranial artery. The primary outcome was any of the following: stroke or death within 30 days of enrollment, ischemic stroke in the territory of the symptomatic intracranial artery beyond 30 days after enrollment, or any stroke or death within 30 days after stenting a patient in the medical group during follow-up. A total of 227 patients were included in the study, 82 of whom were female, and the mean (SD) age was 59.5 (11.8) years. Being female (hazard ratio [HR], 1.9; 95% CI, 0.96-3.7), having diabetes mellitus (HR, 1.8; 95% CI, 0.9-3.5), not taking a statin at enrollment (HR, 2.6; 95% CI, 1.2-5.7), stroke as the qualifying event (HR, 2.5; 95% CI, 1.03-6.0), Rankin grade of 1 or greater (HR, 2.3; 95% CI, 0.9-5.5), old infarct in the territory of the stenotic artery (HR, 2.6; 95% CI, 1.3-5.1), and greater than 80% stenosis (HR, 1.9; 95% CI, 0.9-3.7) were associated (P < .10) with higher risk on bivariate analysis. Factors that were significantly associated with a primary end point on multivariable analyses were old infarct in the territory (HR, 2.6; 95% CI, 1.3-5.3; P = .006), stroke as the qualifying event (HR, 3.0; 95% CI, 1.1-7.7; P = .03), and no statin use at enrollment (HR, 2.4; 95% CI, 1.1-5.2; P = .03). Old infarct in the territory of the stenosis, new stroke presentation, and absence of statin use at enrollment were independently associated with high rates of the primary end point in the medical group in the SAMMPRIS Trial. These features may be useful for selecting high-risk patients for future clinical trials evaluating alternative therapies for intracranial stenosis. clinicaltrials.gov Identifier: NCT00576693.

Stenting Versus Aggressive Medical Management for Symptomatic Vertebral Artery Stenosis

Posterior circulation strokes account for 20% of all strokes (2). Traditional studies cite a 5-year stroke rate ranging from 22%e 35% following an initial vertebrobasilar transient ischemic attack (TIA) or stroke (11, 14). Contrary to traditional beliefs, the overall risk of recurrent stroke in the posterior circulation is similar to the risk after an anterior circulation stroke, and likely higher in the acute phase (8). In one pooled analysis of 359 patients experiencing vertebrobasilar territory TIA or stroke, the 90-day risk of stroke after the presenting event was 9.6% in patients with vertebrobasilar stenosis versus 2.8% in those without (OR 3.7, 95% CI 1.2e11.0, P 1⁄4 0.012) (9). The authors noted a trend that this risk was higher with intracranial vertebrobasilar stenosis than extracranial vertebral stenosis (P 1⁄4 0.06). To mitigate this risk, aggressive medical management incorporating diet and lifestyle modification, control of hypertension, and the usage of statins and antiplatelet agents may be used (3, 5, 16). In addition, multiple individual case series have suggested that stenting vertebrobasilar lesions may be associated with a low-risk profile and subsequently low rates of referable TIAs or strokes (1, 10, 12, 13, 15). A systematic review of stenting symptomatic, atherosclerotic vertebrobasilar disease reported periprocedural TIA, stroke, and death rates of 1.6%, 1.3%, and 0.3%, respectively, across 313 cases with proximal vertebral artery disease (6). Over a mean follow-up period of 14.2 months, the post-treatment annual rate of TIA or stroke in the vertebrobasilar territory was 0.6%. Interestingly, for 283 cases of distal vertebrobasilar stenting, the periprocedural TIA, stroke, and death rates were 0.7%, 10.6% and 3.2%, respectively (6). The annual rate of subsequent vertebrobasilar stroke over a mean follow-up of 13 months after treatment was 1.9%. Thus although patients with symptomatic intracranial vertebrobasilar stenosis may have a greater risk of TIA or stroke without treatment (9), the risk of stenting may also be higher in this group (6). However, more specifically, a subgroup analysis from the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial demonstrated significantly higher periprocedural ischemic events in patients undergoing stenting of the basilar artery as compared with those undergoing stenting of the intracranial internal carotid, middle cerebral, or vertebral artery (7). Before the Vertebral Artery Stenting Trial (VAST) (3), subgroup analyses of 2 randomized control trials comparing stenting of symptomatic arterial stenosis to best medical management demonstrated no benefit of stenting for patients with vertebral artery stenosis (4, 5). In the Carotid And Vertebral Artery Transluminal Angioplasty Study (CAVATAS), 16 patients with

Hemodynamic alterations in unilateral chronic middle cerebral artery stenosis patients and the effect of percutaneous transluminal angioplasty and stenting: a perfusion-computed tomography study.

The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial indicated that most patients with symptomatic intracranial atherosclerosis are not good candidates for percutaneous transluminal angioplasty and stenting (PTAS) because of a higher complication risk than with conservative treatment. However, enrollment of SAMMPRIS patients was based on lesion severity only, without functional imaging. To determine whether perfusion computed tomography (PCT) can effectively evaluate hemodynamic compromise in unilateral chronic middle cerebral artery stenosis and the alterations of hemodynamics after PTAS. In this prospective study, 89 patients with unilateral middle cerebral artery (MCA) stenosis/occlusion were enrolled and classified into four groups according to the degree of stenosis. Cerebral hemodynamics was evaluated by measuring cerebral blood flow (CBF), cerebral blood volume (CBV), and time to peak (TTP) in the ipsilateral and contralateral hemispheres by PCT before and after intervention with PTAS. Differences in hemodynamic parameters before and after intervention were analyzed. Three different hemodynamic patterns were observed in these patients. Patients with severe MCA stenosis (70-99%) or MCA occlusion demonstrated a significant increase of ipsilateral CBV and TTP, indicating hemodynamic compromise. Ten severe stenosis patients with recurrent ischemic symptoms despite of maximal conservative therapy were selected for PTAS. PTAS induced a rapid recovery of cerebral hemodynamics (especially TTP) at 1 week post intervention. PCT appears to be a valuable noninvasive technique to evaluate hemodynamic compromise in unilateral chronic MCA stenosis and the improvements after PTAS.

Association Between Lipoprotein (a) Levels and Vascular Events in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial. (P1.147)

Association Between Lipoprotein (a) Levels and Vascular Events in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial. (P1.147)

Evidence-based optimization of the management of intracranial atherosclerotic disease

Dear Editor,The recently published article in Neurological Sciences byMattioni et al. [1] titled ‘Prevalence of intracranial largeartery stenosis and occlusion in patients with acuteischaemic stroke or TIA’ was very interesting. The authorsretrospectively evaluated all consecutive patients whopresented with an ischemic stroke or transient ischemicattack (TIA) and also underwent computed tomographyangiography (CTA) in the emergency room of a singleinstitution in The Netherlands over a 2-year span. Of the220 patients included for analysis, 39 % were found tohave intracranial atherosclerotic disease (ICAD) including35 % with intracranial arterial occlusion, 6 % with steno-sis, and 2 % with both. Multivariate analysis identifiedonly extracranial carotid disease and partial or total anteriorcirculation syndromes as predictors of symptomatic ICAD.Given the contribution of ICAD to ischemic cerebro-vascular disease, optimizing its management has been thesource of significant debate within the neurological andneurointerventional communities for over a decade. In2005, the warfarin–aspirin symptomatic intracranial dis-ease (WASID) trial showed that warfarin and aspirin eachafforded the same protection from recurrent ischemicstroke or TIA, but warfarin was associated with a higherrate of adverse events [2]. For symptomatic patients whofailed medical therapy, endovascular intervention withangioplasty and stenting began to emerge as a potentialtreatment option [3]. In 2005, the United States Food andDrug Administration approved the Wingspan stent (BostonScientific, Natick, MA, USA) under a humanitarian deviceexemption for the treatment of symptomatic ICAD patientswith at least 50 % stenosis of a major intracranial arterywho were refractory to antithrombotic therapy. InitialICAD stenting outcomes with the Wingspan system werepromising, with excellent rates of technical success andacceptably low complication rates [4]. For the time being,it appeared that the neurointerventional community hadprovided an effective solution for symptomatic ICAD.The initial enthusiasm which accompanied the advent ofstenting for ICAD treatment was quelled in 2011 by thesobering results of the stenting and aggressive medicalmanagement for preventing recurrent stroke in intracranialstenosis (SAMMPRIS) trial, which reported higher rates ofcerebral ischemic events in the intervention cohort com-pared to the medical cohort [5]. The medical therapy inSAMMPRIS was composed of dual antiplatelet therapywith aspirin and clopidogrel combined with aggressivemedical treatment of modifiable risk factors such ashypertension and hyperlipidemia. In the modern era ofICAD management, the options for symptomatic patientswho have failed maximal medical management which istypically the same as the therapy utilized in SAMMPRIS, isat best experimental. Although the enthusiasm for ICADtreatment with stenting has waned following SAMMPRIS,neurointerventionalists have continued to offer this thera-peutic option to carefully selected patients. The currentendovascular strategies for symptomatic ICAD are predi-cated on diminishing the incidence of in-stent restenosis(ISR), which has been shown to be relatively high inpatients treated with the Wingspan stent. The use of closedcell, low radial force devices, such as the Enterprise stent(Cordis Corporation, Miami Lakes, FL, USA), balloon-expandable stents, and drug-eluting stents have all beenreported to reduce the rate of ISR in retrospective case

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.

Abstract W P130: Relationship Between Risk Factor Control and Vascular Events in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) Trial

Background and Purpose: Symptomatic intracranial stenosis patients with poorly controlled cholesterol and blood pressure had an increased risk of vascular events in WASID. Therefore, SAMMPRIS aggressive medical management protocols targeted these risk factors. We sought to determine if intensive risk factor control in SAMMPRIS resulted in lower risk of vascular events during follow-up. Methods: Data on 227 SAMMPRIS patients randomized to aggressive medical management alone were used for these analyses. Vascular risk factors were recorded at baseline, 30 days, and every 4 months. Additional follow-up and close-out visit data were also included. For each patient, values for all risk factor measures (from baseline until the time of an event) were averaged and dichotomized based on the risk factor target. Time to event curves for a vascular event (stroke, MI, and vascular death) were compared between subjects with and without risk factor control using the log-rank test and hazard ratios were calculated with Cox proportional hazards regression. Results: The univariate analyses are shown in the table. Subjects with mean follow-up SBP &lt; 140 mm Hg (&lt; 130 for diabetics), LDL &lt; 70 mg/dL, and at least moderate exercise had lower risk of vascular events compared to those who did not achieve those targets. Control of other risk factors (HgA1c, smoking, non-HDL, and Body Mass Index) did not have a significant impact on outcome. Conclusions: Well controlled SBP and LDL during follow-up were predictors of lower vascular events in SAMMPRIS, confirming that SBP and LDL should be aggressively treated in patients with intracranial stenosis to prevent future vascular events. Exercise participation was also associated with fewer vascular events and should be strongly encouraged.

Abstract T MP105: Relationship Between Compliance With the Lifestyle Modification Program and Risk Factor Control in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) Trial

Background and Purpose: SAMMPRIS was the first vascular disease prevention trial to provide a commercially available lifestyle modification program to subjects to enhance risk factor control. We sought to determine the relationship between compliance with the lifestyle modification 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 &lt; 3 expected lifestyle coaching calls were excluded from these analyses. Subjects with ≥ 78.5% of calls (median % of completed/expected calls) were considered Compliant (n=201). Subjects with &lt; 78.5% and those who refused to participate were considered Noncompliant (n=200). Mean risk factor values or % in-target for each risk factor were compared between Compliant vs. 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 between the groups. Results: As shown in the figure, Compliant subjects had better risk factor control throughout follow-up for LDL, SBP, HgA1c, non-HDL, non-smoking, and exercise than Noncompliant subjects, but there was no difference for BMI. Compliant subjects also had better control of LDL, non-HDL, and HgA1c at baseline. Both groups had some improvement in risk factors throughout the study (except for BMI), but after adjusting for baseline differences between the groups, Compliant subjects had a greater change from baseline than Noncompliant subjects for SBP at 24 months and HgA1c at 6 months. Conclusions: SAMMPRIS subjects who were compliant with the lifestyle modification program had better risk factor control during the study for almost all risk factors.

Abstract T P144: Association Between Lipoprotein (a) Levels and Vascular Events in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial

Background: Lipoprotein (a) (Lp(a)) has been implicated in atherothrombogenesis and prior studies have suggested its pathogenic role in the development of intracranial atherosclerosis (ICAS). Objective: We sought to determine the association between baseline Lp(a) levels and risk of vascular events during follow-up in patients randomized to the medical arm of the SAMMPRIS trial. Methods: Baseline Lp(a) data was available for 226 of 227 patients randomized to the medical arm in SAMMPRIS. High Lp(a) was defined as &gt; 65 mg/dL in Blacks and &gt; 35 mg/dL in Whites and Others. The primary outcome was any ischemic stroke and the secondary outcome was a composite of vascular events (ischemic stroke, MI and vascular death). Kaplan-Meier curves for the time to the outcomes were compared between patients with high and low Lp(a) using the log-rank test. Using Lp(a) as a continuous variable, Cox proportional hazards model was used to determine the association between Lp(a) and time to outcomes of interest. Results: Overall, 17/92 (18.5%) patients with high Lp(a) levels had an ischemic stroke during follow-up versus 24/134 (17.9%) with normal Lp(a) levels, with no difference between the Kaplan-Meier curves of the groups (p=0.94). In a Cox proportional hazards model relating Lp(a) to time to ischemic stroke, Lp(a) was not statistically significant (p = 0.82). Similarly, 23/92 (25%) patients with high Lp(a) levels had a vascular event during follow-up versus 29/134 (21.6%) with normal Lp(a) levels, with no difference between the Kaplan-Meier curves (p=0.58). In a Cox proportional hazards model relating Lp(a) to time to ischemic stroke, MI, or vascular death, Lp(a) was not statistically significant (p = 0.46). Conclusion: Patients with high Lp(a) levels in the SAMMPRIS trial did not have an increased risk of ischemic strokes or vascular events during follow-up. Although prior studies have suggested a pathogenic contribution of high Lp(a) to the development of ICAS, our results do not find an association between high Lp(a) and increased risk of vascular events.