Treatment of carotid stenosis in asymptomatic, nonoctogenarian, standard risk patients with stenting versus endarterectomy trials.

OBJECTIVE: Asymptomatic carotid stenosis is the most frequent indication for carotid endarterectomy (CEA) in the United States. Published trials and guidelines support CEA indications in selected patients with longer projected survival and when periprocedural complications are low. Transfemoral carotid artery stenting with embolic protection (CAS) is a newer treatment option. The objective of this study was to compare outcomes in asymptomatic, nonoctogenarian patients treated with CAS vs CEA. METHODS: Patient-level data was analyzed from 2544 subjects with ≥70% asymptomatic carotid stenosis who were randomized to CAS or CEA in addition to standard medical therapy. One trial enrolled 1091 (548 CAS, 543 CEA) and another enrolled 1453 (1089 CAS, 364 CEA) asymptomatic patients less than 80 years old (upper age eligibility). Independent neurologic assessment and routine cardiac enzyme screening were performed. The prespecified, primary composite endpoint was any stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke within 4 years after randomization. RESULTS: There was no significant difference in the primary endpoint between CAS and CEA (5.3% vs 5.1%; hazard ratio, 1.02; 95% confidence interval, 0.7-1.5; P = .91). Periprocedural rates for the components are (CAS vs CEA): any stroke (2.7% vs 1.5%; P = .07), myocardial infarction (0.6% vs 1.7%; P = .01), death (0.1% vs 0.2%; P = .62), and any stroke or death (2.7% vs 1.6%; P = .07). After this period, the rates of ipsilateral stroke were similar (2.3% vs 2.2%; P = .97). CONCLUSIONS: In a pooled analysis of two large randomized trials of CAS and CEA in asymptomatic, nonoctogenarian patients, CAS achieves comparable short- and long-term results to CEA.

Factors influencing credentialing of interventionists in the CREST-2 trial.

BACKGROUND: The Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) is a pair of randomized trials assessing the relative efficacy of carotid revascularization in the setting of intensive medical management (IMM) in patients with asymptomatic high-grade atherosclerotic stenosis. One of the trials assesses IMM with or without carotid artery stenting (CAS). Given the low risk of stroke in nonrevascularized patients receiving IMM, it is essential that there be low periprocedural risk of stroke for CAS if it is to show incremental benefit. Thus, credentialing of interventionists to ensure excellence is vital. This analysis describes the protocol-driven approach to credentialing of CAS interventionists for CREST-2 and its outcomes. METHODS: To be eligible to perform stenting in CREST-2, interventionists needed to be credentialed on the basis of a detailed Interventional Management Committee (IMC) review of data from their last 25 consecutive cases during the past 24 months along with self-reported lifetime experience case numbers. When necessary, additional prospective cases performed in a companion registry were requested after webinar training. Here we review the IMC experience from the first formal meeting on March 21, 2014 through October 14, 2017. RESULTS: The IMC had 102 meetings, and 8311 cases submitted by 334 interventionists were evaluated. Most were either cardiologists or vascular surgeons, although no single specialty made up the majority of applicants. The median total experience was 130 cases (interquartile range [IQR], 75-266; range, 25-2500). Only 9% (30/334) of interventionists were approved at initial review; approval increased to 46% (153/334) after submission of new cases with added training and re-review. The median self-reported lifetime case experience for those approved was 211.5 (IQR, 100-350), and the median number of cases submitted for review was 30 (IQR, 27-35). The number of CAS procedures performed per month (case rate) was the only factor associated with approval during the initial cycle of review (P < .00001). CONCLUSIONS: Identification of interventionists who were deemed sufficiently skilled for CREST-2 has required substantial oversight and a controlled system to judge current skill level that controls for specialty-based practice variability, procedural experience, and periprocedural outcomes. High-volume interventionists, particularly those with more recent experience, were more likely to be approved to participate in CREST-2. Primary approval was not affected by operator specialty.

Duration of asymptomatic status and outcomes following carotid endarterectomy and carotid artery stenting in the Carotid Revascularization Endarterectomy vs Stenting Trial.

BACKGROUND: Most carotid revascularization studies define asymptomatic as symptom-free for more than 180 days; however, it is unknown if intervention carries similar risk among those currently asymptomatic but with previous symptoms (PS) vs those who were always asymptomatic (AA). METHODS: We compared the periprocedural and 4-year risks of PS vs AA patients in the Carotid Revascularization Endarterectomy vs Stenting Trial (CREST) randomized to carotid endarterectomy (CEA) or carotid artery stenting (CAS)/angioplasty. Proportional hazards models adjusting for age, sex, and treatment were used to assess the risk of periprocedural stroke and/or death (S+D; any S+D during periprocedural period), stroke and death at 4 years (any S+D within the periprocedural period and ipsilateral stroke out to 4 years) and the primary end point at 4 years (any stroke, death, and myocardial infarction within the periprocedural period and ipsilateral stroke out to 4 years). Analysis was performed pooling the CEA-treated and CAS-treated patients, and separately for each treatment. RESULTS: Of 1181 asymptomatic patients randomized in CREST, 1104 (93%) were AA and 77 (7%) were PS. There was no difference in risk when comparing the AA and PS cohorts in the pooled CAS+CEA population for periprocedural S+D (2.0% vs 1.3%), S+D at 4 years (3.6% vs 3.2%), or the primary end point (5.2% vs 5.8%). There were also no differences among those assigned to CEA (periprocedural S+D, 1.5% vs 0%; S+D at 4 years, 2.7% vs 0%; or primary end point, 5.1% vs 2.4%) or CAS (periprocedural S+D, 2.5% vs 2.8%; S+D at 4 years, 4.4% vs 6.9%; or primary end point, 5.3% vs 9.8%) when analyzed separately. CONCLUSIONS: In CREST, only a small minority of asymptomatic patients had previous ipsilateral symptoms. The outcomes of periprocedural S+D, periprocedural S+D, and ipsilateral stroke up to 4 years, and the primary end point did not differ for AA patients compared with PS patients.

Influence of multiple stents on periprocedural stroke after carotid artery stenting in the Carotid Revascularization Endarterectomy versus Stent Trial (CREST).

BACKGROUND: In the Carotid Revascularization Endarterectomy versus Stent Trial (CREST), carotid artery atherosclerotic lesion length and nature of the lesions were important factors that predicted the observed difference in stroke rates between carotid endarterectomy and carotid artery stenting (CAS). Additional patient-related factors influencing CAS outcomes in CREST included age and symptomatic status. The importance of the operator's proficiency and its influence on periprocedural complications have not been well defined. We evaluated data from CREST to determine the impact of use of multiple stents, which we speculate may be related to technical proficiency. METHODS: CREST includes CAS performed for symptomatic ≥50% carotid stenosis and asymptomatic ≥70% stenosis. Both symptomatic and asymptomatic patients were enrolled in the trial and in the lead-in registry. Data from patients enrolled in the CREST registry and randomized trial from 2000 to 2008 were reviewed for patient- and lesion-related characteristics along with number of stents deployed. The occurrence of 30-day stroke and demographic and clinical features were recorded. Odds ratios for 30-day stroke associated with the use of multiple stents were calculated in univariate analysis and on multivariable analysis after adjustment for demographics (age, sex, symptomatic status), lesion characteristics (length, ulceration, eccentric, percentage stenosis), and risk factors (diabetes, hypertension, dyslipidemia, and smoking). RESULTS: The registry (n = 1531) and trial (n = 1121) enrolled 2652 patients undergoing CAS. The mean age was 69 years; 36% were women, and 38% were symptomatic. The mean diameter stenosis was 78%, and the mean lesion length was 18 mm (±standard deviation, 8 mm). Risk factors included hypertension (85%), diabetes (32%), dyslipidemia (84%), and smoking (23%). All patients received Acculink stents (Abbott Vascular, Abbott Park, Ill) that were 20, 30, or 40 mm in length (straight or tapered) and Accunet (Abbot Vascular) embolic protection when possible. Most patients received one stent (n = 2545), whereas 98 patients received two stents and 9 patients received three stents (P < .001) to treat the lesion. Patients receiving more than one stent were older (P = .01) but did not differ in other demographic or risk factors. Strokes occurred in 118 (4.5%) of all CAS procedures, in 102 (4%) with the use of one stent, and in 16 (15%) with the use of two or three stents. After adjustment for demographics, lesion characteristics, and risk factors, the use of more than one stent resulted in 2.90 odds (95% confidence interval, 1.49-5.64) for a stroke. CONCLUSIONS: Although we know that lesion characteristics (length, ulceration) play an important role in CAS outcomes, in this early experience with carotid stenting, a significant and independent relationship existed between the number of stents used and procedural risk of CAS. We postulate that this was an indicator of the operator's inexperience with the procedure.

Interventional cardiologists: Beware and be aware: An updated report of radiation-induced cutaneous cancers.

We describe 5 years of follow-up of a previously reported case of disabling ionizing radiation (IR)-related cutaneous cancer in a high-volume interventional cardiologist. This case illustrates the cycle of exposure, disease, remission, and re-exposure that demonstrates the cause-and-effect relationship between radiation exposure and cutaneous cancer. Prior cautions for working in environments with radiation exposure emphasized strict adherence to the ALARA principle and called for improved radiation protection equipment. New studies stress that radiation exposure should be as near to zero as possible and place a call for research and technologies that mitigate the use of IR for all interventionists.

Early Endarterectomy Carries a Lower Procedural Risk Than Early Stenting in Patients With Symptomatic Stenosis of the Internal Carotid Artery: Results From 4 Randomized Controlled Trials.

BACKGROUND AND PURPOSE: Patients undergoing carotid endarterectomy (CEA) for symptomatic stenosis of the internal carotid artery benefit from early intervention. Heterogeneous data are available on the influence of timing of carotid artery stenting (CAS) on procedural risk. METHODS: We investigated the association between timing of treatment (0-7 days and >7 days after the qualifying neurological event) and the 30-day risk of stroke or death after CAS or CEA in a pooled analysis of individual patient data from 4 randomized trials by the Carotid Stenosis Trialists' Collaboration. Analyses were done per protocol. To obtain combined estimates, logistic mixed models were applied. RESULTS: Among a total of 4138 patients, a minority received their allocated treatment within 7 days after symptom onset (14% CAS versus 11% CEA). Among patients treated within 1 week of symptoms, those treated by CAS had a higher risk of stroke or death compared with those treated with CEA: 8.3% versus 1.3%, risk ratio, 6.7; 95% confidence interval, 2.1 to 21.9 (adjusted for age at treatment, sex, and type of qualifying event). For interventions after 1 week, CAS was also more hazardous than CEA: 7.1% versus 3.6%, adjusted risk ratio, 2.0; 95% confidence interval, 1.5 to 2.7 (P value for interaction with time interval 0.06). CONCLUSIONS: In randomized trials comparing stenting with CEA for symptomatic carotid artery stenosis, CAS was associated with a substantially higher periprocedural risk during the first 7 days after the onset of symptoms. Early surgery is safer than stenting for preventing future stroke. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00190398; URL: http://www.controlled-trials.com. Unique identifier: ISRCTN57874028; Unique identifier: ISRCTN25337470; URL: http://www.clinicaltrials.gov. Unique identifier: NCT00004732.

Carotid angiographic characteristics in the CREST trial were major contributors to periprocedural stroke and death differences between carotid artery stenting and carotid endarterectomy.

OBJECTIVE: The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) demonstrated a higher periprocedural stroke and death (S+D) rate among patients randomized to carotid artery stenting (CAS) than to carotid endarterectomy (CEA). Herein, we seek factors that affect the CAS-CEA treatment differences and potentially to identify a subgroup of patients for whom CAS and CEA have equivalent periprocedural S+D risk. METHODS: Patient and arterial characteristics were assessed as effect modifiers of the CAS-CEA treatment difference in 2502 patients by the addition of factor-by-treatment interaction terms to a logistic regression model. RESULTS: Lesion length and lesions that were contiguous or were sequential and noncontiguous extending remote from the bulb were identified as influencing the CAS-to-CEA S+D treatment difference. For those with longer lesion length (≥12.85 mm), the risk of CAS was higher than that of CEA (odds ratio [OR], 3.42; 95% confidence interval [CI], 1.19-9.78). Among patients with sequential or remote lesions extending beyond the bulb, the risk for S+D was higher for CAS relative to CEA (OR, 9.01; 95% CI, 1.20-67.8). For the 37% of patients with lesions that were both short and contiguous, the odds of S+D in those treated with CAS was nonsignificantly 28% lower than for CEA (OR, 0.72; 95% CI, 0.21-2.46). CONCLUSIONS: The higher S+D risk for those treated with CAS appears to be largely isolated to those with longer lesion length and/or those with sequential and remote lesions. In the absence of those lesion characteristics, CAS appears to be as safe as CEA with regard to periprocedural risk of S+D.

Agreement between site-reported and ultrasound core laboratory results for duplex ultrasound velocity measurements in the Carotid Revascularization Endarterectomy versus Stenting Trial.

OBJECTIVE: Patients in the Carotid Revascularization Endarterectomy vs Stenting Trial (CREST) had duplex ultrasound (DU) scans prior to treatment and during follow-up to document the severity of carotid disease and the anatomic outcome of carotid endarterectomy (CEA) or carotid artery stenting (CAS). An ultrasound core laboratory (UCL) reviewed DU data from the clinical sites. This analysis was done to determine the agreement between site-reported and UCL-verified DU velocity measurements. METHODS: Clinical site DU worksheets, B-mode images, and Doppler velocity waveforms for the treated carotid arteries were reviewed at the UCL. The highest internal carotid artery peak systolic velocity (PSV) and associated Doppler angle were verified. If the angle was misaligned by >3 degrees, it was remeasured at the UCL and the PSV was recalculated. Agreement for PSV was defined as site-reported PSV within ± 5% of UCL-verified PSV. Transcription errors were corrected by the UCL but were not considered as disagreements. Follow-up analysis was limited to patients who received the assigned treatment. RESULTS: The UCL reviewed 1702 prior-to-treatment and 1743 12-month follow-up DU scans (873 CEA, 870 CAS) from 111 clinical sites. Site-reported and UCL-verified PSV agreed in 1124 (66%) of the prior-to-treatment scans and 1200 (69%) of the follow-up scans. In those cases with a disagreement, Doppler angle accounted for disagreement in 339 (59%) of the prior-to-treatment scans and 277 (51%) of the follow-up scans. Based on a threshold PSV for ≥ 70% stenosis of ≥ 230 cm/s on the prior-to-treatment scans and ≥ 300 cm/s on the follow-up scans, UCL review resulted in reclassification of stenosis severity in 75 (4.4%) of the prior-to-treatment scans and 13 (0.75%) of the follow-up scans. There is evidence that the proportion of reclassification at follow-up was greater for CAS (10 scans; 1.2%) than for CEA (three scans; 0.34%) (P = .057). CONCLUSIONS: There was a high rate of agreement between site-reported and UCL-verified DU results in CREST, and UCL review was associated with a low rate of stenosis reclassification. However, angle alignment errors were quite common and prompted recalculation of velocity in 20% of prior-to-treatment scans and 18% of follow-up scans. The use of a UCL provides a uniform process for DU interpretation and can identify sources of error and suggest technical improvements for future studies.

Restenosis after carotid artery stenting and endarterectomy: a secondary analysis of CREST, a randomised controlled trial.

BACKGROUND: In the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), the composite primary endpoint of stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke thereafter did not differ between carotid artery stenting and carotid endarterectomy for symptomatic or asymptomatic carotid stenosis. A secondary aim of this randomised trial was to compare the composite endpoint of restenosis or occlusion. METHODS: Patients with stenosis of the carotid artery who were asymptomatic or had had a transient ischaemic attack, amaurosis fugax, or a minor stroke were eligible for CREST and were enrolled at 117 clinical centres in the USA and Canada between Dec 21, 2000, and July 18, 2008. In this secondary analysis, the main endpoint was a composite of restenosis or occlusion at 2 years. Restenosis and occlusion were assessed by duplex ultrasonography at 1, 6, 12, 24, and 48 months and were defined as a reduction in diameter of the target artery of at least 70%, diagnosed by a peak systolic velocity of at least 3·0 m/s. Studies were done in CREST-certified laboratories and interpreted at the Ultrasound Core Laboratory (University of Washington). The frequency of restenosis was calculated by Kaplan-Meier survival estimates and was compared during a 2-year follow-up period. We used proportional hazards models to assess the association between baseline characteristics and risk of restenosis. Analyses were per protocol. CREST is registered with ClinicalTrials.gov, number NCT00004732. FINDINGS: 2191 patients received their assigned treatment within 30 days of randomisation and had eligible ultrasonography (1086 who had carotid artery stenting, 1105 who had carotid endarterectomy). In 2 years, 58 patients who underwent carotid artery stenting (Kaplan-Meier rate 6·0%) and 62 who had carotid endarterectomy (6·3%) had restenosis or occlusion (hazard ratio [HR] 0·90, 95% CI 0·63-1·29; p=0·58). Female sex (1·79, 1·25-2·56), diabetes (2·31, 1·61-3·31), and dyslipidaemia (2·07, 1·01-4·26) were independent predictors of restenosis or occlusion after the two procedures. Smoking predicted an increased rate of restenosis after carotid endarterectomy (2·26, 1·34-3·77) but not after carotid artery stenting (0·77, 0·41-1·42). INTERPRETATION: Restenosis and occlusion were infrequent and rates were similar up to 2 years after carotid endarterectomy and carotid artery stenting. Subsets of patients could benefit from early and frequent monitoring after revascularisation. FUNDING: National Institute of Neurological Disorders and Stroke and Abbott Vascular Solutions.

The Carotid Revascularization Endarterectomy versus Stenting Trial: credentialing of interventionalists and final results of lead-in phase.

The success of carotid artery stenting in preventing stroke requires a low risk of periprocedural stroke and death. A comprehensive training and credentialing process was prerequisite to the randomized Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) to assemble a competent team of interventionalists with low periprocedural event rates. Interventionalists submitted cases to a multidisciplinary Interventional Management Committee. This committee evaluated 427 applicants. Of these, 238 (56%) were selected to participate in the training program and the lead-in phase, 73 (17%) who had clinical registry experience and satisfactory results with the devices used in CREST were exempt from training and were approved for the randomized phase, and 116 (27%) did not qualify for training. At 30 days in the lead-in study, stroke, myocardial infarction, or death occurred in 6.1% of symptomatic subjects and 4.8% of asymptomatic subjects. Stroke or death occurred in 5.8% of symptomatic subjects and 3.8% of asymptomatic subjects. Outcomes were better for younger subjects and varied by operator training. Based on experience, training, and lead-in results, the Interventional Management Committee selected 224 interventionalists to participate in the randomized phase of CREST. We believe that the credentialing and training of interventionalists participating in CREST have been the most rigorous reported to date for any randomized trial evaluating endovascular treatments. The study identified competent operators, which ensured that the randomized trial results fairly contrasted outcomes between endarterectomy and stenting.

One-year clinical outcomes, midterm survival, and predictors of mortality after carotid stenting in elderly patients.

BACKGROUND: It has been demonstrated recently that carotid stenting can be performed safely in patients > or =80 years of age. However, it is uncertain whether these patients will derive benefit because longevity after revascularization is an important consideration. This study was conducted to determine survival and predictors of mortality of selected elderly patients after stenting. METHODS AND RESULTS: One hundred forty-two consecutive elderly patients who were non-high risk for stenting underwent 153 procedures. Patients had either symptomatic stenosis > or =50% or asymptomatic stenosis > or =70%. Demographics and in-hospital outcomes were entered into a database; subsequent outcomes and mortality data were obtained retrospectively. Mean+/-SD age was 83.3+/-3.1 years. Symptomatic patients accounted for 28%. Overall survival at 3 years was 76% (85% at 2 years). At 1 year, 1 fatal stroke had occurred, with 97% of survivors (n=114) free of neurological events (neurological status was undetermined in the remaining 3%). Predictors of mortality were remote (> or =6 months) transient ischemic attack or cerebrovascular accident, smoking history, and creatinine clearance (hemoglobin level showed a strong trend toward achieving significance); for the asymptomatic subgroup, predictors of mortality were smoking history, previous carotid endarterectomy, hemoglobin level, and increasing age. In particular, symptom status and sex were not independent predictors of mortality. CONCLUSIONS: This study demonstrates that in selected elderly patients, a high proportion (85%) survived 2 years and >75% survived 3 years after stenting. Carotid stenting may be considered a revascularization option in such patients. Better selection of patients using the predictors of mortality may help to reduce unwarranted procedures and to optimize survival likelihood.

Minimal contrast use in carotid stenting: avoiding contrast pitfalls.

BACKGROUND: The progression of endovascular approaches to vascular disease has led to an increasing volume of procedures requiring iodinated contrast media. Accordingly, the potential for contrast-induced nephropathy (CIN) also continues to increase. Hypotension, independent of contrast use, is a well-described cause of acute renal dysfunction and an important factor in endovascular procedures complicated by hypotension. CIN is the third leading cause of hospital-acquired acute renal failure, accounting for 12% of cases, and the frequency of CIN in coronary angiography ranges from 5% in patients with mild renal insufficiency to 50% in those with severe renal dysfunction and diabetes. Prior carotid trials have demonstrated that patients with dialysis-dependent renal failure had a stroke, death and myocardial infarction rate of 28.6%. CIN is an economic burden with increased morbidity, length of hospitalization, chronic renal impairment and higher mortality. Multiple pharmacological agents have been studied as prophylaxis to CIN, but none have been shown to be beneficial, including a recent meta-analysis of 13 randomized N-acetylcysteine trials showing inconclusive efficacy. The preprocedural avoidance of nephrotoxic drugs, iso- or low-osmolar contrast, reduced volume contrast and additional intravenous fluids are all recommended as strategies in reducing the risk of CIN.

Carotid artery stenting is associated with increased complications in octogenarians: 30-day stroke and death rates in the CREST lead-in phase.

BACKGROUND: A heightened risk of stroke and death among octogenarians undergoing carotid artery stenting (CAS) has been reported. The multicenter Carotid Revascularization Endarterectomy vs. Stent Trial (CREST) supported by the National Institute of Neurological Disorders, National Institutes of Health, compares the efficacy of carotid endarterectomy (CEA) and CAS in an ongoing clinical trial. This effort also includes a "lead-in" phase of symptomatic (>50% stenosis) and asymptomatic (>70% stenosis) patients. The protocol calls for patients to receive aspirin and clopidogrel before and 30-days after CAS and to be examined by a study neurologist preprocedure, at 24-hours, and at 30-day. The occurrence of stroke and death was reviewed by an independent clinical events committee. METHODS: The association of age and periprocedural stroke and death was examined in 749 lead-in patients undergoing CAS (30.7% symptomatic, 69.3% asymptomatic). Patients were separated into four age categories: less than 60, 60 to 69, 70 to 79, and 80 years or older, and the proportion of patients with stroke and death during the 30-day periprocedural period was calculated for each category. RESULTS: An increasing proportion of patients suffered stroke and death with increasing age (P = .0006); 2 (1.7%) of 120 patients under age 60, 3 (1.3%) of 229 aged 60 to 69, 16 (5.3%) of 301 aged 70 to 79, and 12 (12.1%) of 99 patients aged 80 years and older. These increasingly high complication rates at older ages were not mediated by adjustment for symptomatic status, use of antiembolic devices, gender, percentage of carotid stenosis, or the presence of distal arterial tortuosity. CONCLUSIONS: Interim results from the lead-in phase of CREST show that the periprocedural risk of stroke and death after CAS increases with age in the course of a credentialing registry. This effect is not mediated by potential confounding factors. Randomized trial data are needed to compare the CAS versus CEA periprocedural risk of stroke and death by age. Pending results from randomized studies, care should be taken when CAS is performed in older patient populations.

Credentialing of surgeons as interventionalists for carotid artery stenting: experience from the lead-in phase of CREST.

BACKGROUND: Credentialing of vascular surgeons to perform carotid artery stenting (CAS) continues to be a major issue confronting the specialty of Vascular Surgery. Cannulation of aortic arch branches, and placement of carotid antiembolic devices and stents constitute the major technical challenges to vascular surgeons becoming credentialed to perform CAS. The multicenter Carotid Revascularization Endarterectomy vs Stenting Trial (CREST), supported by the National Institute of Neurological Disorders and Stroke, National Institute of Health, reviews credentials of interventionalists, including surgeons, for the trial's "lead-in" phase of CAS to treat symptomatic (>50% stenosis) and asymptomatic (>70% stenosis). METHODS: Vascular surgeons requesting participation in CREST must have achieved basic interventional credentialing criteria as recommended by the Society of Vascular Surgery. Each interventionalist is asked to submit notes and narrative summaries from a series of 10 to 30 CAS procedures for review by a multi-specialty review committee before being approved to participate in CREST. Thereafter, during the lead-in phase of CREST, each approved interventionalist is asked to perform CAS procedures using the study devices in as many as 20 patients. In this interim report from the CREST lead-phase, the association of specialty of operator (vascular surgeon, neurosurgeon, other specialist) and periprocedural stroke and death rate was examined in patients undergoing CAS. In addition, current enrollment volume in the lead-in phase by specialty of the principal investigator was examined. RESULTS: Thirty-two of 134 (23.9%) CREST-credentialed interventionalists are vascular surgeons (n = 22; 16.4%) or neurosurgeons (n = 10; 7.5%). For events monitored through March 31, 2004, 789 patients had undergone CAS procedures performed by these 134 specialists. Thirty-day stroke and death rate was 4.6%, and myocardial infarction was observed in 1.1% of patients. Serious adverse events have not been clustered at individual institutions, and no significant differences have been observed between vascular surgeons or neurosurgeons and other credentialed specialists. CONCLUSIONS: Vascular surgeons with basic catheter and guide wire skills, particularly those who have incorporated diagnostic cerebral angiography into their practice, can be credentialed to perform CAS. Individuals or groups should devote a number of cases (n = 10-30 per surgeon) to CAS to accomplish this goal. Pending US Food and Drug Administration approval of devices and Center for Medicaid and Medicare Services reimbursement, institutional financial support for the performance of these procedures must be secured. The learning curve for CAS should not be considered so formidable as to discourage surgeons from adding these techniques of CAS to their procedural inventory.

Advanced c-myc antisense (AVI-4126)-eluting phosphorylcholine-coated stent implantation is associated with complete vascular healing and reduced neointimal formation in the porcine coronary restenosis model.

An advanced six-ring morpholino backbone c-myc antisense (AVI-4126) was shown to inhibit c-myc expression and intimal hyperplasia after local catheter delivery in a porcine balloon injury model. The purpose of this study was to investigate the effects of an AVI-4126-eluting phosphorylcholine-coated (PC) stent on c-myc expression restenosis and vascular healing after stent implantation in porcine coronary arteries. PC stents were loaded with AVI-4126 using soak trap. Nine pigs underwent AVI-4126 PC coronary stent implantation (two stents/animal). Two to six hours postprocedure, three pigs were sacrificed and stented segments were analyzed by Western blot for c-myc expression. In chronic experiments, six pigs (12 stent sites) were sacrificed at 28 days following intervention and vessels were perfusion-fixed. High-performance liquid chromatography analysis of plasma samples showed minimal presence of the antisense. Western blot analysis of the stented vessels demonstrated inhibition of c-myc expression at 2 and 6 hr after procedure. Quantitative histologic morphometry showed that the neointimal area was significantly reduced (by 40%) in the antisense-coated group compared with control (2.3 +/- 0.7 vs. 3.9 +/- 0.8 mm(2), respectively; P = 0.0077). Immunostaining and electron microscopy demonstrated complete endothelialization, without fibrin deposition, thrombosis, or necrosis in all implanted stents. In the porcine coronary model, an advanced c-myc-eluting PC stent blocked c-myc expression and significantly inhibited myointimal hyperplasia and allowed complete reendothelialization and healing response.

First human experience with the 17-beta-estradiol-eluting stent: the Estrogen And Stents To Eliminate Restenosis (EASTER) trial.

OBJECTIVES: The purpose of the study was to examine the safety and efficacy of 17-beta-estradiol-eluting stent implantation on coronary de novo lesions. BACKGROUND: Recent animal data indicate that local delivery of 17-beta-estradiol promotes re-endothelialization, inhibits cell migration and proliferation, and prevents restenosis. METHODS: A total of 30 consecutive patients underwent 17-beta-estradiol-eluting BiodVysio (Biocompatibles Ltd., London, United Kingdom) stent implantation for the treatment of coronary de novo lesions. Clinical, angiographic, and intravascular ultrasound (IVUS) analysis was performed at six-month follow-up. RESULTS: All stents were successfully deployed and patients were discharged home without clinical events. A total of two patients exceeded 50% intra-stent narrowing by angiography, whereas no patients experienced edge restenosis. One patient had focal intra-stent restenosis (60% diameter stenosis) with no symptoms and negative stress test, whereas the other patient had diffuse restenosis, requiring target vessel revascularization. No other patient experienced any major adverse cardiac event. Follow-up IVUS revealed a neointimal hyperplasia volume of 32.3 +/- 16.4 mm(3), whereas the stent volume was 143.7 +/- 43.7 mm(3), resulting in a neointimal volume obstruction of 23.5 +/- 12.5%. None of the patients had > or =50% volume obstruction by IVUS. CONCLUSIONS: Implantation of 17-beta-estradiol-eluted BiodVysio stents appears feasible and safe, showing low rates of binary restenosis and revascularization. These results warrant further confirmation with a large, randomized multicenter trial.

Paclitaxel prevented restenosis in a totally occluded small vessel with in-stent restenosis: a 9-month angiographic follow-up.

We present a case of a 57-year-old patient who underwent multiple percutaneous coronary interventions for a lesion at the graft anastomosis to his first obtuse marginal branch. After initial angiographic success with multiple treatment modalities (excluding intravascular brachytherapy because of prior mantle radiation), restenosis or reocclusion eventuated on each occasion. Two paclitaxel-coated stents were implanted in this small vessel with diffuse in-stent restenosis and recurrent total occlusion. Complete patency was documented on a 9-month angiographic follow-up.