Stenting And Angioplasty With Protection In Patients At High Risk For Endarterectomy Research Articles

Abstract 16929: Defining Thresholds for Meaningful 30-day Health Status Changes Following Transfemoral Carotid Artery Stenting

Introduction: Carotid artery stenosis treatment trials have focused on clinical endpoints such as stroke, death, and MI, but evidence of carotid revascularization’s impact on health status is limited. This study aims to establish minimal clinically important differences (MCIDs) to assess clinical improvement or worsening from the perspectives of patients with carotid artery stenosis undergoing transfemoral carotid artery stenting (TF-CAS). Methods: We studied patients in the multicenter Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) registry who underwent TF-CAS between 2010 and 2014 and who completed either the EQ-5D-3L or SF-36, two generic health-related quality-of-life surveys. Distribution-based MCIDs were calculated as 0.5 standard deviations for 30-day changes in health status scores post-TF-CAS for the EQ-5D-3L index value and visual analog scale (VAS) subscales and the SF-36 mental and physical component summary (MCS and PCS) subscales. We then stratified this analysis by symptom status (presence or abscence of prior stroke or TIA). Results: The study included 3,930 patients (27.7% symptomatic) who completed the EQ-5D-3L and 3,018 (30.5% symptomatic) who completed the SF-36. The MCIDs for the overall cohorts were 0.09, 11.02, 4.73, and 5.39 for the EQ-5D-3L index value, EQ-5D-3L VAS, SF-36 MCS, and SF-36 PCS, respectively. All MCIDs are summarized in Table 1. The MCIDs for each subscale were similar between asymptomatic and symptomatic subpopulations. Conclusions: Distribution-based thresholds for improvement and worsening of health status in patients undergoing TF-CAS were established for commonly-used generic health status instruments. These reference values can be used in both symptomatic and asymptomatic disease and will be important for interpreting future trial results focusing on the benefit of TF-CAS from patients’ perspectives.

The less invasive paradox, why carotid artery stenting is not suitable for the high-risk patient.

Carotid artery stenosis causes significant morbidity and mortality accounting for approximately 8% of all ischaemic strokes. Carotid artery stenting (CAS) offers an endovascular alternative to carotid endarterectomy (CEA), suggested as a viable option in those deemed high-risk for open CEA due to comorbidities or operative technical considerations. A number of large randomised-controlled trials (RCTs) and meta-analysis comparing CAS vs. CEA in unselected patient populations support the conclusion that CAS is associated with a higher risk of stroke and CEA is associated with a higher risk of myocardial infraction. Initial promise for CAS in high-risk patients was demonstrated by The Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial that reported CAS was non-inferior to CEA. However, there is evidence to suggest age-related adverse outcome in patients undergoing CAS. There is limited evidence to suggest that CEA could be suitable even in patients deemed high-risk for medical or technical reasons. Further contemporary research on the use of CAS and CEA in high-risk patients is required to re-evaluate current guidelines and high-risk criterion. It is common for a composite outcome of death, ipsilateral stroke and MI which should be questioned as subsequent quality of life is likely to differ after suffering a stroke in comparison to MI. This literature review will discuss the current evidence for CAS and CEA interventions in unselected populations and high-risk patients with carotid disease requiring intervention.

Outcomes after carotid artery stenting in Medicare beneficiaries, 2005 to 2009.

Despite increased carotid artery stenting (CAS) dissemination following the 2005 National Coverage Determination, to our knowledge, periprocedural and long-term outcomes have not been described among Medicare beneficiaries. To describe the incidence of outcomes during and after the periprocedural period among Medicare beneficiaries undergoing CAS. Observational study with a mean follow-up time of approximately 2 years among 22,516 fee-for-service Medicare beneficiaries at least 66 years old undergoing CAS (2005-2009) who were linked to the Centers for Medicare & Medicaid Services' CAS database. Database procedure dates were required to fall during a Medicare hospitalization for CAS. Periprocedural (30-day) and long-term risks of mortality and stroke or transient ischemic attack, as well as periprocedural myocardial infarction. Subgroups were based on sociodemographic, clinical, and center-level factors, as well as the Stenting and Angioplasty With Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial or Carotid Revascularization Endarterectomy vs Stenting Trial (CREST) enrollment criteria. The mean patient age was 76.3 years, 60.5% were male, 93.8% were of white race, 91.2% were at high surgical risk, 47.4% were symptomatic, and 97.4% had carotid stenosis of at least 70%. Crude 30-day mortality, stroke or transient ischemic attack, and myocardial infarction risks were 1.7% (95% CI, 1.5%-1.8%), 3.3% (95% CI, 3.0%-3.5%), and 2.5% (95% CI, 2.3%-2.7%), respectively. Mortality during a mean follow-up time of 2 years was 32.0% (95% CI, 31.0%-33.0%), with rates of 37.3% (95% CI, 35.8%-38.7%) among symptomatic patients and 27.7% (95% CI, 26.4%-28.9%) among asymptomatic patients. Older age, symptomatic carotid stenosis, and nonelective hospital admission were associated with increased adjusted hazards of mortality and stroke or transient ischemic attack during and after the periprocedural period. The presence of a stroke center, government ownership, and a hospital bed capacity of 500 or more were associated with increased adjusted hazards of periprocedural mortality and stroke or transient ischemic attack. Few patients met the SAPPHIRE trial or CREST enrollment criteria primarily because physicians did not meet proficiency requirements either due to exceeding periprocedural complication trial thresholds or not meeting minimum CAS volume requirements. Competing risks may limit the benefits of CAS in certain Medicare beneficiaries, particularly among older and symptomatic patients who have higher periprocedural and long-term mortality risks. The generalizability of trials like the SAPPHIRE or CREST to the Medicare population may be limited, underscoring the need to evaluate real-world effectiveness of carotid stenosis treatments.

Preoperative Coronary Stenosis Is a Determinant of Early Vascular Outcome after Carotid Endarterectomy.

Background and PurposeThe benefit of carotid endarterectomy (CEA) is directly influenced by the risk of perioperative adverse outcomes. However, patient-level risks and predictors including coronary stenosis are rarely evaluated, especially in Asian patients. The aim of this study was to determine the relationship between the vascular risk factors underlying CEA, including coronary stenosis, and postoperative outcome.MethodsOne hundred and fifty-three consecutive CEAs from our hospital records were included in this analysis. All patients underwent coronary computed tomography angiography before CEA. Data were analyzed to determine the vascular outcomes in patients with mild-to-moderate vs. severe coronary stenosis and high vs. standard operative risk, based on the criteria for high operative risk defined in the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial. The vascular outcome was defined as the occurrence of postoperative (≤30 days) stroke, myocardial infarction (MI), or death.ResultsAn adverse vascular outcome occurred in 8 of the 153 CEAs, with 6 strokes, 2 MIs, and 3 deaths. The vascular outcome differed significantly between the groups with mild-to-moderate and severe coronary stenosis (p=0.024), but not between the high- and standard-operative-risk groups (stratified according to operative risk as defined in the SAPPHIRE trial). Multivariable analysis adjusting for potent predictors revealed that severe coronary stenosis (odds ratio, 6.87; 95% confidence interval, 1.20-39.22) was a significant predictor of the early vascular outcome.ConclusionsSevere coronary stenosis was identified herein as an independent predictor of an adverse early vascular outcome.

Treatment of Symptomatic Carotid Stenosis: Carotid Stent Placement Versus Endarterectomy

The mainstay of treatment options for symptomatic carotid stenosis is focused around medical management, carotid endarterectomy, and carotid angioplasty and stent placement. The International Carotid Stenting Study (ICSS), also called Carotid and Vertebral Artery Transluminal Angioplasty Study 2 (CAVATAS 2), the Stent-Supported Percutaneous Angioplasty of the Carotid Artery Versus Endarterectomy (SPACE) trial, the Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S) trial, the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial, and the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) were five major trials which compared carotid endarterectomy and carotid angioplasty and stent placement. We review the results of the trials and incorporation of the results into clinical decision making.

Postoperative Cardiac Damage After Standardized Carotid Endarterectomy Procedures in Low- and High-Risk Patients

We conducted a comparison of postoperative cardiac damage, defined as cardiac troponin I (cTn-I) elevation, after carotid endarterectomy in low- and high-risk patients. The Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) criteria for stratifying patients considered for carotid endarterectomy into low and high surgical risk groups were used prospectively. All patients had preoperative full cardiologic evaluations and cTn-I value assessments that were repeated on postoperative days 1, 3, and 7. Postoperative cTn-I values ranging from 0.05 to 0.5 ng/mL were classified as myocardial ischemia; values >0.5 ng/mL were classified as myocardial infarction. Mortality was 1.2%, the stroke rate was null, and symptomatic myocardial infarction was null. Among the 56 high-risk patients, 8 had cTn-I values>0.5 ng/mL. Among the 106 low-risk patients, 10 patients had cTn-I value >0.5 ng/mL and 4 patients had cTn-I values that were >0.05 ng/mL and ≤0.5 ng/mL. All patients with increased cTn-I levels were asymptomatic. Concerning all patients, the mean preoperative cTn-I value was 0.007 ng/mL, which increased to 0.438 ng/mL on postoperative day 1 (P=0.017), 0.168 ng/mL on postoperative day 3 (P=0.06), and 0.019 ng/mL on postoperative day 7 (P=0.02). In the high-risk group, the mean preoperative cTn-I value was 0.008 ng/mL, which increased to 0.829 ng/mL on postoperative day 1, 0.270 ng/mL on postoperative day 3, and 0.030 ng/mL on postoperative day 7. In the low-risk group, the mean preoperative cTn-I value was 0.007 ng/mL, which increased to 0.198 ng/mL on postoperative day 1, 0.119 ng/mL on postoperative day 3, and 0.013 ng/mL on postoperative day 7. Patients without cardiac damage showed analogous tendencies in their troponin values. Comparison of troponin values between high- and low-risk patients on each day showed no statistical difference. Electrocardiogram alterations were seen in 20 of the 22 patients with asymptomatic troponin elevation but in none without troponin elevation. Carotid endarterectomy is followed by an increase in cTn-I value>0.5 ng/mL in 14% of all cases, although symptomatic cardiac ischemia is very low. However, high-risk patients as defined by the SAPPHIRE criteria do not show an increased risk of cardiac damage compared to low-risk patients. Larger studies using cTn-I as a marker of postoperative cardiac damage, after carotid endarterectomy or stenting, are needed.

Abstract TP156: Re-analysis of the SAPPHIRE and CREST Trials Using Weighted Composite Endpoints

Background: Composite endpoints were used in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) and Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trials to compare outcomes between those who underwent carotid artery stent (CAS) placement and those who underwent carotid endarterectomy (CEA) for treatment of carotid artery disease (CAD). However, using composite endpoints assumes that each individual outcome is of equal clinical importance. Objective: To determine if there was a difference in effectiveness between CAS and CEA in treating CAD if weighted composite endpoints were used in the two randomized trials. Methods: Long-term results were examined for each trial (3 years for SAPPHIRE and 4 years for CREST). Each outcome was given a weighted measure based on a point system [death=5; major stroke=4; minor stroke=2; and myocardial infarction=1]. Study populations were amplified by using a constant coefficient (sum of all points=12). Results were then compared between the CAS and CEA groups to determine statistical significance. Results: At 3 years, there were a total of 56 and 67 adverse outcomes in the CAS and CEA groups, respectively, in the SAPPHIRE trial. At 4 years, there were a total of 215 and 190 adverse outcomes in the CAS and CEA groups, respectively, in the CREST trial. Based on weighted composite endpoints, the CAS group had a significantly lower rate of adverse outcomes compared to the CEA group in the SAPPHIRE trial (p<0.0001) but a significantly higher rate of adverse outcomes in the CREST trial (p<0.0001). Conclusion: With the use of weighted composite endpoints, one can provide more clinically relevant information by discriminating among adverse outcomes and describing differences with greater discriminatory power. Based on weighted composite endpoints, there is clear superiority of CAS over CEA in the SAPPHIRE trial, but the converse is true of results from the CREST trial.

Risk Prediction for Adverse Events After Carotid Artery Stenting in Higher Surgical Risk Patients

The goal of carotid artery stenting is to decrease the risk of stroke or other adverse events from carotid artery disease. Choosing a treatment strategy requires patient-specific information regarding periprocedural risk of adverse neurologic events. The aim of this study was to predict individual patient risk after carotid artery stenting in patients at higher risk for carotid endarterectomy. Subjects enrolled in the Stenting and Angioplasty with Protection in Patients at High-Risk for Endarterectomy (SAPPHIRE) worldwide study underwent carotid artery stenting with distal protection. Only patients with at least 1 anatomic or comorbid factor associated with elevated surgical risk were included. Preprocedural factors were used to develop a model and integer-based risk score predicting stroke or death within 30 days. The model was calibrated and internally validated using bootstrap resampling. Ten thousand one hundred eighty-six patients were included in the analysis. The overall rate of stroke or death was 3.6% at 30 days after carotid artery stenting. Independent predictors of adverse outcomes were increased age (P=0.006), history of stroke (P<0.001), history of transient ischemic attack presentation (P=0.001), recent (<4 weeks) myocardial infarction (P=0.006), dialysis treatment (P=0.007), need for cardiac surgery in addition to carotid revascularization (P=0.005), a right-sided carotid stenosis (P=0.006), a longer carotid plaque (P=0.012), the presence of a Type II or III aortic arch (P=0.035), and a tortuous carotid arterial system (P=0.004). The optimism-adjusted C-statistic was 0.691. Commonly collected clinical and anatomic variables can identify patients at high and low risk for stroke or death after carotid artery stenting.

Outcomes of carotid artery stenting in high-risk patients; a single center retrospective review

In our study, we evaluated the safety and efficacy of carotid artery stenting(CAS) in high surgical risk patients. 22 consecutive patients who underwent carotid artery stenting(CAS) between March 2009 and December 2011 were eligible. Only symptomatic stenosis were studied in high surgical risk patients as defined by the SAPPHIRE(Stenting and Angioplasty with Protection in Patients at High-Risk for Endarterectomy) trial. The mean age was 77.8 (range 67-87). Of the study group, 17 male(77.27%) and 5 female(22, 72%). Procedural success was achieved in 21 patients(95.4%). The mean stenosis in patients was 90.68 ±5.4%. Reasons for stenting included cardiac/pulmonary risk(63%), contralateral carotid artery occlusion(72%), age older than 75(72%). None of the patients suffered from major stroke, MI or death due to CAS during their hospital stay. The overall rate of in-hospital adverse events (TIA, permanent bradycardia, hypotension) was 18.1 %(4 of 21). Bradycardia in 2(9.5%), hypotension in one(4.7%) and transient ischemic attack in one(4.7%) were observed during procedures. Our results support the use of CAS in high surgical risk patients with significant symptomatic carotid artery disease.

Distal Protection Device-Induced Slow- or Stop-Flow Phenomenon During Carotid Stenting and the Use of Aspiration to Decrease Periprocedural Events

The phenomenon of slow flow (significant reduction in antegrade flow in the internal carotid artery [ICA]) or stop flow (cessation of antegrade flow in the ICA) during carotid artery stenting (CAS) caused by distal embolic protection devices (EPDs), specifically the Angioguard XP filter, was evaluated in the article by Sorimachi et al. (12) in this issue of WORLD NEUROSURGERY. Although this is not a well-discussed topic in the literature, it could have very important implications with respect to the acceptance of CAS because this acceptance depends on the equivalent effectiveness of CAS when compared to its operative counterpart, carotid endarterectomy, in preventing periprocedural stroke. CAS has been criticized for its higher periprocedural event rates when compared to carotid endarterectomy. These events mainly occur during stent placement and angioplasty, although they have been shown to occur up to 18 hours after the procedure (13). The use of a distal EPD can potentially reduce the incidence of intracranial embolization observed during CAS, decreasing periprocedural event rates. The literature includes multiple studies that show lower stroke rates with distal EPDs as well as studies that show no statistical difference when they are used, such as the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) trial (5). However, the most recent trial published, the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST), which was a multicenter randomized North American trial that compared the efficacy of carotid endarterectomy with that of CAS, performed with the aid of an EPD in the prevention of stroke, myocardial infarction, and death in symptomatic and asymptomatic patients, showing a very low 30-day composite rate of stroke and death for symptomatic (6.1%) and asymptomatic (3.8%) CAS patients (3). Other studies have looked at the slow-flow phenomenon during CAS, such as Casserly et al. (4), who used multivariate logistic regression analysis to evaluate 71 CAS procedures. Their analysis showed that increased age, history of transient ischemic attack or stroke within 6 months of the procedure, and large stent diameter were predictive of slow flow during CAS. Slow flow was noted predominantly after balloon dilatation, although 25% of the cases occurred after stent deployment (4). The underlying etiology of slow flow is uncertain, but it is known that once the filter is retrieved, normal flow is restored. This isolates the filter as the problem and, thus, likely the occlusion of the pores of the filter as the reason for the slow-flow state. Histopathologic analysis of the filter debris has shown amorphous material derived from the core of atherosclerotic plaque (1). This correlates with the findings of slow flow being related to stent deployment and balloon angioplasty, as well as symptomatic lesions and increased stent diameter being independent predictors of slow-flow states. Casserly et al. (4) found that the 30-day incidence of stroke and/or death among patients with slow flow was 9.5%, compared to 2.9% in patients with normal flow. All the strokes occurred the same day as the procedure and were noted after retrieval of thefilter. These risk factors of slowflow have also been shown to be general risk factors of neurologic events associated with CAS. The CREST trial showed that patients older than age 79 years had higher 30-day stroke and death rates (11.9%) (8). Both the CREST (3) and the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE)

Health-Related Quality of Life Following Carotid Stenting Versus Endarterectomy: Results From the SAPPHIRE (Stenting and Angioplasty with Protection in Patients at HIgh Risk for Endarterectomy) Trial

This study compared health-related quality of life in patients undergoing carotid artery stenting (CAS) versus surgical endarterectomy (CEA). Carotid artery stenting is approved in the U.S. for treating carotid stenosis in patients at high surgical risk. Whether CAS offers advantages in terms of other patient-centered outcomes is unknown. We evaluated health-related quality of life in the SAPPHIRE (Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy) trial, which randomized 334 high-risk patients with carotid stenosis to CAS versus CEA. Health status assessments were obtained at baseline; 2 weeks; and 1, 6, and 12 months after revascularization. Generic measures included the Short-Form-36 (SF-36) (0 to 100 scale), general health rating, and EuroQol (EQ-5D). In addition, we used 6 disease-specific modified Likert scales to assess difficulty with walking, eating/swallowing, driving, headaches, neck pain, and leg pain. In patients treated according to protocol (n = 159 CAS; n = 151 CEA), CAS patients had better scores at 2 weeks for the SF-36 role physical scale (mean difference: 9.0; 95% confidence interval: 0.9 to 17.1; p = 0.031), but these differences had resolved by 1-month follow-up. For the disease-specific scales, CAS patients reported less difficulty eating/swallowing at 2 weeks, less difficulty driving at 2 weeks, and less neck pain at 2 weeks; each of these differences between groups was no longer present at 1 month. No other scores differed between groups at any time point. Among patients at high surgical risk, CAS was associated with less health status impairment during the first 2 weeks of recovery when compared with CEA. However, these differences had resolved by 1 month after the procedure, and no other differences between revascularization strategies in health-related quality of life were found.

Outcomes of Carotid Artery Stenting in High-Risk Patients With Carotid Artery Stenosis

Carotid artery angioplasty and carotid artery stenting (CAS) offer a viable alternative to carotid endarterectomy for symptomatic and asymptomatic patients; however, the complication rates associated with CAS may be higher than previously documented. We evaluated the safety and efficacy of CAS in high surgical risk patients in a single neurovascular center retrospective review. An institutional review board-approved retrospective review of the clinical variables and treatment outcomes of 101 consecutive patients (109 stents) from July 2001 to March 2007 with carotid stenosis were analyzed. Both symptomatic and asymptomatic stenoses were studied in high surgical risk patients as defined by the SAPPHIRE (Stenting and Angioplasty with Protection in Patients at High-Risk for Endarterectomy) trial. Specifically, those patients with clinically significant cardiac disease (congestive heart failure, abnormal stress test, or need for open-heart surgery), severe pulmonary disease, contralateral carotid occlusion, contralateral laryngeal nerve palsy, recurrent stenosis after carotid endarterectomy, previous radical neck surgery, or radiation therapy to the neck, and an age older than 80. Seventy-four percent of the patients were symptomatic (n = 81), and the mean stenosis in symptomatic patients was 83%. Reasons for stenting included cardiac/pulmonary/medical risk (60%), contralateral internal carotid artery occlusion (8%), recurrent stenosis after carotid endarterectomy (11%), carotid dissection (6%), age older than 80 (7%), previous radical neck surgery (7%), and previous neck radiation (1%). Stent deployment was achieved in 108 of 109 vessels (99%). Distal embolic protection devices were used in 72% of cases treated. The overall rate of in-hospital adverse events (transient ischemic attack, intracranial hemorrhage, minor stroke, major stroke, myocardial infarction, and death) was 8.3% (9 of 109). Of these events, 2 patients (1.8%) experienced a hemispheric transient ischemic attack (neurological symptoms that resolved within 24 hours), 2 others (1.8%) had transiently symptomatic acute reperfusion syndrome. The 30-day stroke/death/myocardial infarction risk was 4.6% (n = 5). Of these patients, 3 had minor strokes (2.7%) defined as a modified Rankin Scale score less than 3 at 1-year follow-up, 1 had a major stroke (0.9%) defined as a modified Rankin Scale score of 3 or more at 1-year follow-up, and 1 patient died after a periprocedural myocardial infarction (0.9%). CAS can be performed with a low 30-day complication rate, even with a higher percentage of symptomatic lesions. The results support the use of CAS in high surgical risk patients with both significant symptomatic and asymptomatic carotid artery disease.

Carotid artery stenting: A systematic review of randomized clinical trials

Carotid occlusive disease is responsible for a significant proportion of major adverse cardiovascular events (death, stroke, myocardial infarction). Effective prevention by means of revascularization is a sufficient treatment, if performed at a center with an acceptably low procedural complication rate. Carotid surgery is the currently accepted standard of treatment for revascularization of extra cranial carotid occlusive disease. This has been validated by randomized clinical trials that have demonstrated its efficacy over best medical therapy. However, less invasive protected carotid artery stenting (CAS) has emerged as a potential therapeutic alternative to carotid endarterectomy (CEA) for the treatment of carotid atherosclerotic disease. Over the past decade several clinical trials have compared endovascular with surgical treatment. The Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial favored stenting over surgery in high-risk patients. The effectiveness of endovascular treatment in low-risk patients and patients with asymptomatic stenoses at preventing of stroke is still uncertain. Carotid artery stenting with an embolic protection device cannot be considered a scientifically sound and evidence-based alternative to carotid surgery in low-risk and asymptomatic patients until we have the results of further randomized trials. This overview presents the currently available data from randomized trials.

Outcomes after carotid endarterectomy: Is there a high-risk population? A National Surgical Quality Improvement Program report

Carotid endarterectomy (CEA) is the standard treatment of carotid stenosis for symptomatic and asymptomatic patients. Carotid angioplasty and stenting (CAS), however, has been proposed as alternative therapy for patients deemed at high-risk for CEA. This study examined 30-day adjudicated outcomes in a contemporary series of CEAs and assessed the validity of criteria used to define a potential high-risk patient population for CEA. Patients undergoing isolated CEA in private sector hospitals between Jan 1, 2005, and Dec 31, 2006, were identified using the prospectively gathered National Surgical Quality Improvement Program database. The primary study end points were 30-day stroke and death rates. Demographic, preoperative, and intraoperative variables were examined using multivariate models to identify variables associated with the study end points. Variables used to define systemic "high-risk" patients in the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) study (active cardiac disease, severe chronic obstructive pulmonary disease, and octogenarian status) were examined individually and in composite fashion for association with study endpoints. Of the 3949 CEAs performed, 59% were in men, 30% were "high-risk" (19% age >80), and 43% had a previous neurologic event. The 30-day stroke rate was 1.6%, the death rate was 0.7%, and combined stroke/death rate was 2.2%. Multivariate analysis showed that intraoperative transfusion (odds ratio [OR], 5.95; 95% confidence interval [CI], 1.71-20.66; P = .005), prior major stroke (OR, 5.34; 95% CI, 2.96-9.64; P < .0001), shorter height (surrogate for small artery size; OR, 1.09; 95% CI, 1.02-1.16; P = .010), and increased anesthesia time (OR, 1.02; 95% CI, 1.00-1.03; P = .008) were predictive of stroke. Critical limb ischemia (OR, 12.72; 95% CI, 3.49-46.40; P < .0001) and poor functional status (OR, 7.05; 95% CI, 2.95-16.82; P < .0001) were independent correlates of death. Systemic high-risk variables, either combined or individually, did not increase risk of stroke or death on multivariate analysis. CEA is associated with favorable 30-day outcomes across a spectrum of patient comorbidity features including octogenarian status. Anatomic and technical features are the important predictors of perioperative stroke, whereas critical limb ischemia and poor functional status are important predictors of death for patients undergoing CEA. These data refute the concept that CAS is preferred for patients deemed high-risk by virtue of systemic comorbidities.

Atherosclerotic Peripheral Vascular Disease Symposium II

Carotid artery disease is a major cause of ischemic stroke, the risk of which is directly related to the severity of stenosis and presence of symptoms.1,2 Stroke is the third leading cause of death in the United States, with approximately three quarters of a million strokes per year. Stroke is the leading cause of functional impairment, with more than 20% of survivors requiring institutional care and up to one third having a permanent disability.3 More worrisome, however, is the fact that as the population ages, the number of patients having strokes appears to be increasing.4 The pathophysiology of stroke may be broadly classified as hemorrhagic, embolic, or ischemic. The majority of strokes are caused by embolic events due to atheroemboli from the carotid artery, the ascending aorta, and arch vessels or cardiac thromboembolism from the left atrium or ventricle. It is estimated that carotid artery stenosis is responsible for 15% to 20% of all strokes.5 As percutaneous treatment options expand, there is uncertainty about appropriate therapy for carotid disease. This document will focus on 3 current controversies: (1) carotid artery revascularization in asymptomatic patients, (2) carotid artery stenting (CAS) in patients who are considered to be at increased surgical risk for carotid endarterectomy (CEA), and (3) the current role for CAS in patients at average surgical risk. ### Prevalence and Natural History The prevalence of asymptomatic extracranial carotid stenosis (≥50%) in persons >65 years of age is estimated to be between 5% and 10%, whereas ≤1% of patients are estimated to have a severe narrowing (>80%).6 In asymptomatic patients with ≥50% carotid artery stenoses, the annual risk of stroke is between 1% and 4.3%.2,7 Long-term (10- to 15-year) cohort studies in asymptomatic patients with moderate to severe carotid stenosis demonstrate an ipsilateral stroke rate between 0.9% and 1.1% per …

Long-term results of 442 consecutive, standardized carotid endarterectomy procedures in standard-risk and high-risk patients

The objectives of this study were to determine the results of a specific technique in the performance of carotid endarterectomy (CEA) and to compare results using this technique between standard-risk and high-risk patients eligible for Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) and between asymptomatic and symptomatic patients. A total of 391 patients underwent 442 consecutive CEA procedures under general anesthesia with the intent to shunt, patch, and perform intraoperative completion duplex ultrasound imaging. Indications included 272 asymptomatic patients (61.5%) with carotid stenoses > or =60% and 170 symptomatic patients (38.5%) with carotid stenosis > or =50%. Data were analyzed to determine the early (< or =30 days) and long-term morbidity and mortality overall in standard-risk and high-risk procedures and in asymptomatic and symptomatic patients. The primary end points were the occurrence of all strokes or death or myocardial infarction (MI) in the first 30 postoperative days (100% follow-up) and the occurrence by life-table analysis of ipsilateral stroke or death or MI (SDMI) out to 93 months (mean, 31.4 months). A total of 441 (99.7%) procedures included shunting, 440 (99.5%) included patching, and 442 (100%) had completion duplex ultrasound imaging. Of these, 235 procedures were standard risk and 207 procedures were high risk. At the 30-day follow-up, there were two ipsilateral central neurologic deficits (1 major stroke, 1 minor stroke), no death, and one MI (0.45% for all strokes or death; 0.68% for all strokes or death or MI). After 30 days of follow-up, an additional 16 strokes (9 ipsilateral, 7 contralateral), eight MIs, and 38 deaths had occurred. No statistically significant difference was found between standard-risk and high-risk groups or between asymptomatic and symptomatic groups for stroke, death, MI, stroke or death, or stroke or death or MI at 30 days or during long-term follow-up at any interval up to 93 months. CEA performed with intent to treat using general anesthesia, shunting, patching, and completion duplex scanning results in extremely low 30-day and long-term morbidity and mortality in asymptomatic, symptomatic, standard-risk and high-risk patients. These results are substantially superior to those reported in carotid stenting trials for both carotid stenting and CEA and do not support the contention that there is a high-risk group for CEA.

Carotid Stents: Unleashed, Unproven

Primarily on the basis of data derived from the Stenting and Angioplasty With Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial,1 the US Food and Drug Administration (FDA) has approved the use of carotid stents (CASs) in high-risk patients. The SAPPHIRE trial was published and much heralded as a randomized trial demonstrating that CASs were not inferior to carotid endarterectomy (CEA). Yet, the more recent Endarterectomy Versus Angioplasty in Patients with Symptomatic Carotid Stenosis randomized trial of CASs compared with CEA had to be stopped because the stroke rate with stents was so high that it triggered the safety guidelines of the study design.2 How can we explain the striking difference in outcome between these 2 studies, and how did it happen that the FDA was so convinced of the quality and validity of the SAPPHIRE trial that it granted approval for CASs? An examination of the SAPPHIRE trial—its conduct, data collection and analysis, the circumstances of publication, the presentation to the FDA Advisory Panel, and its consequent approval—is the primary focus of this article. This is a case study of the flaws in our system for the evaluation and approval of medical devices that warrant serious reflection on our ability to properly create and act on accurate information and live up to our commitment to evidence-based decision making. Response by Samuelson et al p 1601 As it now stands, existing studies leave us with the unfortunate but not unreasonable conclusion that no scientific basis exists for the use of CASs as approved by the FDA, and in the absence of change, there is every reason to doubt the capability of our current system to protect the public from unnecessary risk in the future. Although this article focuses on just 1 example of how our systems …

The Argument to Support Broader Application of Extracranial Carotid Artery Stent Technology

As new technology becomes available, the stent technique for the extracranial carotid artery continues to evolve into a safer, more effective therapy for stroke prevention. With the availability of embolic protection, improved stent designs, and added endovascular physician experience, outcomes for carotid artery stenting (CAS) now consistently parallel those for carotid endarterectomy (CEA). Although carotid endarterectomy was established as the gold standard for carotid revascularization, the available scientific evidence must continue to be interpreted in the context of further advancements in nearly all related areas of medicine. One multicenter randomized trial and several nonrandomized registries have successfully established the CAS indications for patients with high surgical risk and have provided evidence to support the use of CAS techniques in patients with low surgical risk. Clinicians must continue to improve their understanding of patient-specific factors and conduct research that will refine indications while optimizing current medical therapy and that will integrate CAS and carotid endarterectomy as complementary treatments. Response by LoGerfo p 1610 The outcomes for CAS have been improving over the past 10 years and now appear nearly equivalent to those for CEA. In fact, many historical similarities are seen in the development of these 2 techniques. Although CEA was established as the gold standard for extracranial carotid revascularization, the available scientific evidence must continue to be interpreted in the context of further advancements in nearly all related areas of medicine. The current research comparing CAS and CEA has not shown a clinically robust and statistically significant difference between the 2 treatments. When differences do exist, clinicians must continue to refine patient-specific indications and to conduct further research to understand these complex risk-benefit analyses in the context of advanced medical treatments and complementary revascularization techniques. The following review details the argument to support implementation of CAS technology for athero-occlusive carotid …

Radiation arteritis: A contraindication to carotid stenting?

Carotid artery stenting (CAS) for high-risk anatomic lesions is accepted practice. Neck irradiation and radiotherapy-induced arteritis are common indications. The clinical outcomes of CAS for radiation arteritis have been poorly defined. A prospective database of patients undergoing CAS at a tertiary referral academic medical center was maintained from 1999 to 2006. Patients undergoing primary carotid artery stenting for significant atherosclerotic (ASOD) and radiotherapy (XRT)-induced occlusive disease were analyzed. Life-table analyses were performed to assess time-dependent outcomes. Cox proportional hazard analysis or Fisher's exact test was performed to identify factors associated with outcomes. Data are presented as the mean +/- SEM unless otherwise indicated. During the study period, 150 patients underwent primary CAS, 75% with embolic protection. Fifty-eight percent were symptomatic. One hundred twenty-seven (85%) were treated for ASOD, and 23 (15%) had XRT. The 30-day all-cause mortality rate was 1% for ASOD and 0% for XRT (P = NS); overall survival at 3 years was equivalent. There was no significant difference in major adverse event rates as defined by the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) trial between the groups. The 3-year neurologic event-free rate was 85% for ASOD and 87% for XRT (P = NS). Late asymptomatic occlusions were seen only in XRT patients. The 3-year freedom from restenosis rate was significantly worse for the XRT group, at 20%, vs 74% for the ASOD group (P < .05). Likewise, the 3-year patency rate was also worse for the XRT group, at 91%, vs 100% for ASOD by Kaplan-Meier analysis (P < .05). No factor was predictive of occlusion or stenosis by Cox proportional hazards analysis. CAS for radiation arteritis has poor long-term anatomic outcome and can present with late asymptomatic occlusions. These findings suggest that these patients require closer postoperative surveillance and raise the question of whether CAS is appropriate for carotid occlusive lesions caused by radiation arteritis.

Invited commentary

Invited commentary