Patrick Verta

The CAPTURE registry: Results of carotid stenting with embolic protection in the post approval setting

Background: Pivotal study data examining carotid stenting with embolic protection as a less invasive alternative to endarterectomy for high surgical risk patients have been acquired under controlled conditions with highly selected physicians and hospitals. This report examines outcomes of carotid stenting post‐approval after diffusion of this technology to a broader cross‐section of physicians and hospitals. Methods: The Carotid Acculink/Accunet Post‐Approval Trial to Uncover Unanticipated or Rare Events (CAPTURE) is a prospective, multi‐center registry to assess two important aspects of the post‐IDE experience: the safety of carotid stenting by physicians with varying levels of experience as a measure of the adequacy of physician training, and the identification of rare/unexpected device‐related complications. The primary endpoint was a composite of death, any stroke, or myocardial infarction within 30 days post‐procedure. Results: 3,500 patients were enrolled by 353 physicians at 144 sites. The 30‐day primary endpoint event rate was 6.3% (95% CI: 5.5–7.1%) and did not differ among the three operator experience levels (5.3%, 6.0%, and 7.4%; P = 0.31) from most to least experienced, respectively. There were no differences in outcomes among physician specialties when adjusted for case mix. There were no unanticipated device related adverse events. Conclusions: The results of the CAPTURE study compare favorably to those achieved in the predicate pivotal investigations, and suggest that the post‐approval transfer of this new therapy to the community practice setting via carotid stent training programs is effective in preparing physicians with varying experience levels and specialty training backgrounds.

The CAPTURE registry: Predictors of outcomes in carotid artery stenting with embolic protection for high surgical risk patients in the early post-approval setting

The use of carotid artery stenting with embolic protection has been practiced for over a decade in the United States, and increasingly so since carotid stenting received FDA approval in 2004. While there have been attempts at establishing predictors of outcomes in carotid artery stenting, they have generally been limited to single center experiences and/or multicenter retrospective surveys. This report examines predictors of outcomes in carotid stenting in the earliest and largest prospective multicenter neurologist‐adjudicated experience in the United States post device approval.

First clinical trial of nitinol self-expanding everolimus-eluting stent implantation for peripheral arterial occlusive disease

BACKGROUND A novel self-expanding drug-eluting stent was designed to slowly release everolimus to prevent restenosis following peripheral arterial intervention. The purpose of the first-in-human Superficial Femoral Artery Treatment with Drug-Eluting Stents (STRIDES) trial was to evaluate the safety and efficacy of this device for the treatment of symptomatic superficial femoral and proximal popliteal arterial occlusive disease. METHODS AND RESULTS One hundred four patients were enrolled at 11 European investigative centers in a prospective, nonrandomized, single-arm trial. The patients had severe symptomatic vascular disease, including a significant proportion of patients with critical limb ischemia (17%), diabetes (39%), and single-vessel outflow (26%). The mean lesion length was 9.0 ± 4.3 cm. Ninety-nine percent of patients were available for 12-month follow-up, including duplex imaging in 90% and arteriography in 83%. Clinical improvement, defined as a sustained decrease in Rutherford-Becker clinical category, was achieved in 80% of patients. Primary patency (freedom from ≥50% in-stent restenosis) was 94 ± 2.3% and 68 ± 4.6% at 6 and 12 months, respectively. Plain radiographic examination of 122 implanted devices at 12 months revealed no evidence for stent fracture. CONCLUSIONS The everolimus-eluting self-expanding nitinol stent can be successfully implanted in patients with severe peripheral arterial disease with favorable outcomes and clinical improvements observed in the majority of patients.

Thirty-Day Outcomes for Carotid Artery Stenting in 6320 Patients From 2 Prospective, Multicenter, High-Surgical-Risk Registries

Background—The American Heart Association has established guidelines for acceptable 30-day death and stroke rates for patients with severe carotid disease undergoing standard-risk carotid endarterectomy: <3% for asymptomatic lesions and <6% for symptomatic lesions. To date, carotid artery stenting has not demonstrated these outcomes in multicenter, prospective assessments of high-surgical-risk patients. Methods and Results—Data from 2 prospective, multicenter (280 US sites, 672 operators), postmarket surveillance studies in high-surgical-risk patients were analyzed: 2145 patients from the Emboshield and Xact Post Approval Carotid Stent Trial (EX) and 4175 patients from the Carotid ACCULINK/ACCUNET Post Approval Trial to Uncover Rare Events (C2). Both studies had pre- and postprocedure neurological evaluation and independent adjudication of neurological events. The overall 30-day death and stroke rate was 4.1% (95% CI, 3.3% to 5.0%) for EX and 3.4% (95% CI, 2.9% to 4.0%) for C2. In the population comparable with American Heart Association guidelines (<80 years), the combined 30-day death and stroke rate was 5.3% (95% CI, 3.6% to 7.4%) for symptomatic patients and 2.9% (95% CI, 2.4% to 3.4%) for asymptomatic patients, independent of unfavorable risk factors (anatomic or physiologic); in patients ≥80 years, this rate was 10.5% (95% CI, 6.3% to 16.0%) and 4.4% (95% CI, 3.3% to 5.7%), respectively. In subjects with anatomic features unfavorable for surgery, the 30-day death and stroke rates were 1.7% (95% CI, 0.0% to 8.9%) and 2.7% (95% CI, 1.3% to 4.9%) for symptomatic and asymptomatic cohorts, respectively, independent of age. Conclusions—Outcomes for carotid artery stenting in nonoctogenarian high-surgical-risk patients have improved since the pivotal Food and Drug Administration approval trials, and have achieved American Heart Association standards in both symptomatic and asymptomatic lesions.

The CAPTURE registry - Analysis of strokes resulting from carotid artery stenting in the post approval setting: Timing, location, severity, and type

Background:Although previous reports of carotid stenting with embolic protection (CAS) have focused on clinical outcomes of death, stroke and myocardial infarction, there are few data available characterizing the strokes that occur during CAS, thus limiting understanding of potential mechanisms. This report examines the timing, location, severity, and type of strokes occurring with CAS in the Carotid ACCULINK/ACCUNET Post Approval Trial to Uncover Unanticipated or Rare Events (CAPTURE) study. Methods:CAPTURE is a prospective, multicenter registry conducted to assess outcomes of CAS in the postapproval setting after device approval. A neurologist examined the patients before the procedure, at 24 hours and 30 days post-procedure. The primary end point was a composite of death, any stroke, or myocardial infarction within 30 days post-procedure. Strokes and all neurologic events suspected to be strokes were adjudicated by an independent Clinical Events Adjudication Committee using prespecified definitions. Source documents of all patients with strokes in this cohort were reviewed. Results:The 30-day results were available for 3500 patients. The 30-day primary end point event rate of death, stroke, and myocardial infarction was 6.3% (95% confidence interval: 5.5%–7.1%), and the rate of major stroke and death was 2.9% (95% confidence interval: 2.4 to 3.5). 4.8% of patients experienced a stroke (3.9% ipsilateral and 0.9% nonipsilateral, 2% major). A majority of stroke symptoms (57.7%) were noted post-procedure and pre-discharge, whereas 22.3% were noted during the procedure and 20% postdischarge. A similar timing distribution regardless of preprocedural symptomatic status was found. Overall, 41% (69 of 170) of all strokes were major. The incidence of major strokes was statistically significantly greater among symptomatic compared with asymptomatic patients, 4.6% (22 of 482) and 1.6% (47 of 3018), respectively. There were more minor than major strokes in asymptomatic patients (63% vs. 37%; P = 0.10), whereas stroke severity was equally distributed in symptomatic patients. Among the ipsilateral strokes, almost half (44%) were major, whereas only one-quarter (26%) of the nonipsilateral strokes were major. Overall, 23% of the major strokes were hemorrhagic and 94% of these strokes were noted on the ipsilateral side. There was a tendency toward more major hemorrhagic strokes in symptomatic than in asymptomatic patients (36% vs. 17%; P = 0.07). Fifty-four percent of the strokes post-procedure and pre-discharge were major, whereas 27% of the strokes postdischarge were major. Furthermore, 65% of hemorrhagic strokes were noted post-procedure and pre-discharge, 30% postdischarge. Conclusions:Strokes related to CAS seem to become clinically apparent after the procedure but before discharge in the majority of events. Nevertheless, a significant minority of stroke symptoms follows discharge from the hospital, typically after 24 hours. Timing of stroke after CAS seems to be similar to timing of stroke after carotid endarterectomy. Moreover, nearly 1 in 5 strokes occur in a nonipsilateral distribution, with the exception of intraprocedural events, which were all ipsilateral to the stent being implanted. Hemorrhagic stroke seemed to be more prevalent in the strokes occurring in the post-procedure period. These descriptors of stroke severity, location, and timing may provide insight in to the mechanistic causes of adverse neurologic outcomes in CAS.

30-Day Outcomes for Carotid Artery Stenting in 6,320 Patients From Two Prospective, Multicenter, High Surgical Risk Registries

Background—The American Heart Association has established guidelines for acceptable 30-day death and stroke rates for patients with severe carotid disease undergoing standard-risk carotid endarterectomy: <3% for asymptomatic lesions and <6% for symptomatic lesions. To date, carotid artery stenting has not demonstrated these outcomes in multicenter, prospective assessments of high-surgical-risk patients. Methods and Results—Data from 2 prospective, multicenter (280 US sites, 672 operators), postmarket surveillance studies in high-surgical-risk patients were analyzed: 2145 patients from the Emboshield and Xact Post Approval Carotid Stent Trial (EX) and 4175 patients from the Carotid ACCULINK/ACCUNET Post Approval Trial to Uncover Rare Events (C2). Both studies had pre- and postprocedure neurological evaluation and independent adjudication of neurological events. The overall 30-day death and stroke rate was 4.1% (95% CI, 3.3% to 5.0%) for EX and 3.4% (95% CI, 2.9% to 4.0%) for C2. In the population comparable with American Heart Association guidelines (<80 years), the combined 30-day death and stroke rate was 5.3% (95% CI, 3.6% to 7.4%) for symptomatic patients and 2.9% (95% CI, 2.4% to 3.4%) for asymptomatic patients, independent of unfavorable risk factors (anatomic or physiologic); in patients ≥80 years, this rate was 10.5% (95% CI, 6.3% to 16.0%) and 4.4% (95% CI, 3.3% to 5.7%), respectively. In subjects with anatomic features unfavorable for surgery, the 30-day death and stroke rates were 1.7% (95% CI, 0.0% to 8.9%) and 2.7% (95% CI, 1.3% to 4.9%) for symptomatic and asymptomatic cohorts, respectively, independent of age. Conclusions—Outcomes for carotid artery stenting in nonoctogenarian high-surgical-risk patients have improved since the pivotal Food and Drug Administration approval trials, and have achieved American Heart Association standards in both symptomatic and asymptomatic lesions.

Significant reduction in systolic blood pressure following renal artery stenting in patients with uncontrolled hypertension: Results from the HERCULES trial†

Background: Atherosclerotic renal artery stenosis (ARAS) causes hypertension (HTN) and threatens renal function (RF). The HERCULES Trial is a prospective, multicenter trial of renal stenting in patients with uncontrolled HTN and ARAS evaluating the safety and effectiveness of the RX Herculink Elite Renal Stent System (Abbott Vascular, Santa Clara, CA). Methods: A total of 202 patients (241 total lesions; 78 bilateral lesions) were enrolled between August 2007 and October 2009. The primary endpoint was 9‐month binary restenosis determined by duplex ultrasound and/or angiography. Secondary endpoints included changes in blood pressure, antihypertensive medications, and RF between baseline and 9 months. Brain natriuretic peptide (BNP) was measured at baseline, 24 hr and 30 days postprocedure. Results: Mean systolic blood pressure (SBP) at baseline was 162 mm Hg. Nearly 70% of patients were receiving three or more antihypertensive medications (mean 3.4 medications per patient). Baseline serum creatinine was 1.2 ± 0.4 and 61.5% of subjects had estimated glomerular filtration <60. The restenosis rate was 10.5% at 9 months. The study device, procedure, and clinical success rates were 96.0, 99.2, and 98.0%, respectively. Freedom from major adverse events was 94.8%. At 9 months, the mean SBP significantly decreased (mean 145, paired t test P < 0.0001) after stenting with no change in medications. There was no correlation between SBP reduction and baseline BNP or BNP reduction. Conclusions: HERCULES demonstrates clinically and statistically significant SBP reduction in patients with uncontrolled HTN, low in‐stent restenosis, and complication rates. This study highlights that when appropriate patients are selected for renal artery stenting, impressive reductions in blood pressure may be anticipated. Although the magnitude of absolute reduction in SBP was related to baseline SBP, elevated baseline BNP levels were not predictive of reduction in SBP. Further studies for predictors of clinical response following percutaneous renal revascularization are needed.

Results of carotid artery stenting with distal embolic protection with improved systems: Protected Carotid Artery Stenting in Patients at High Risk for Carotid Endarterectomy (PROTECT) trial

OBJECTIVE The Protected Carotid Artery Stenting in Patients at High Risk for Carotid Endarterectomy (PROTECT) study was performed to evaluate the safety and effectiveness of two devices for carotid artery stenting (CAS) in the treatment of carotid artery stenosis in patients at high risk for carotid endarterectomy (CEA): (1) a new embolic protection device, the Emboshield Pro (Abbott Vascular, Abbott Park, Ill), using the periprocedural composite end point of 30-day death, stroke, and myocardial infarction (DSMI), and (2) a carotid stent in conjunction with an embolic protection device (EPD) using the DSMI periprocedural composite end point plus ipsilateral stroke at up to 3 years for long-term evaluation. METHODS This prospective, multicenter clinical trial enrolled 220 consecutive participants between November 29, 2006, and January 14, 2008, followed by a second cohort of 102 participants between January 14 and June 18, 2008. Enrolled participants had carotid stenosis (symptomatic >50% or asymptomatic >80%). The first 220 subjects underwent distal EPD placement with a new large-diameter filter, and the second cohort of 102 underwent placement of an older EPD that is no longer manufactured. All 322 participants were to be treated with a dedicated carotid stent with a tapered, small, closed-cell design (Xact; Abbott Vascular) and were to be included in the long-term evaluation. Independent neurologic assessment was performed before CAS and at 1 day, 30 days, and annually after CAS. All primary end point events were independently adjudicated by a central committee. RESULTS The periprocedural composite end point of DSMI (95% confidence interval) in the first 220 participants was 2.3% (0.74%, 5.22%), with a combined death and stroke rate of 1.8% (0.50%, 4.59%) and a rate of death and major stroke of 0.5% (0.01%, 2.51%). As of January 3, 2011, the median follow-up for the entire 322-subject cohort for the long-term evaluation was 2.8 years. Freedom from the periprocedural composite of DSMI plus ipsilateral stroke thereafter was 95.4%, with an annualized ipsilateral stroke rate of 0.4%. CONCLUSIONS CAS outcomes in patients at high risk for CEA have improved from earlier carotid stent trials. With periprocedural rates of DSMI of 2.3%, death or stroke at 1.8%, and death or major stroke rate of 0.5%, PROTECT has the lowest rate of periprocedural complications among other comparable single-arm CAS trials in patients at high risk for CEA.

CAPTURE 2 risk-adjusted stroke outcome benchmarks for carotid artery stenting with distal embolic protection

OBJECTIVE Many medical procedures undergo rapid evolution and process of care improvements after introduction. National outcome standards are useful to help physicians, institutions, and other stakeholders evaluate the quality of their programs and take action when suboptimal outcomes are identified. The purpose of this analysis was to derive contemporary risk-adjusted stroke rates from a large, contemporary, independently assessed outcome database within 30 days after carotid artery stenting (CAS) in the United States. METHODS The second phase of carotid ACCULINK/ACCUNET post approval trial to uncover rare events (CAPTURE 2) is an ongoing prospective, multicenter, clinical trial conducted to assess CAS outcomes in the general practice setting after device approval for high surgical risk patients (symptomatic with >50% stenosis or asymptomatic with >80% stenosis). A neurologist examined the patients before the procedure, at 1 day and 30 days after CAS. The primary endpoint was a composite of death, any stroke, or myocardial infarction (MI) within the periprocedural period. Strokes and neurologic events suspected to be strokes were adjudicated by an independent clinical events adjudication committee. Logistic regression analysis including stepwise logistic and multivariable modeling was performed to determine clinical predictors of periprocedural stroke outcome and generate a parsimonious model that could be used for a clinical standard. RESULTS Five thousand two hundred ninety-seven consecutive patients (5297) had CAS performed by 459 physicians at 186 sites before the data cutoff of January 10, 2009. The 30-day rate of stroke was 2.7% (95% confidence interval [CI], 2.3-3.2). Multivariable predictors of periprocedural stroke included age, symptomatic status, and dwell time of embolic protection device. A parsimonious model P(i) = 1/(1+e (-(-3.83 + 0.51 x (symptomatic) + 0.31 x (age >or=80) + 0.62 x (age >or=80 x symptomatic))), including symptomatic and octogenarian status and the term of the interaction of the two, was established based on consideration of clinical predictors, clinical interaction, and practicability. CONCLUSION CAS outcomes in patients at high surgical risk have comparable periprocedural outcomes to published randomized trials of endarterectomy for patients at standard surgical risk. A model is presented for calculating a contemporary national standard for risk-adjusted stroke rates. Quality improvement measures could be based on relative performance to this benchmark and could improve overall outcomes for patients undergoing CAS.

Overview of the 2011 Food and Drug Administration Circulatory System Devices Panel Meeting on the ACCULINK and ACCUNET Carotid Artery Stent System

The Circulatory System Devices Panel of the Medical Devices Advisory Committee to the US Food and Drug Administration (FDA) was convened on January 26, 2011, to review the application by Abbott Vascular (Santa Clara, CA) for a post–market approval supplement (PMA-s) to extend the indications for use of their ACCULINK Carotid Stent System. The stent system had received FDA approval in 2004 for patients at high risk for adverse events after carotid endarterectomy (CEA). Abbott Vascular was seeking to extend its approval to patients at standard risk for CEA on the basis of the data and outcomes derived from the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST; ClinicalTrials.gov Identifier NCT00004732). Herein are presented the essential elements of that day-long meeting. ### Study Conception and Timeline The organizational work on the CREST project was initiated in 1996 by the projects executive committee, which first published on its concept, rationale, and design in 1997.1 The experiential basis for the trial was chiefly 2 small stenting registries in high-surgical-risk, symptomatic patients totaling ≈200 procedures and reporting mortality rates of up to 3% and stroke rates of between 3% and 6%.2,3 The CREST executive committee recognized the novel nature and early stage of the technique, and in accordance with the tenets of clinical equipoise, as well as to provide reassurance to randomizing physicians that a reasonable safety of carotid artery stenting (CAS) had been established at an operator level and across sites, a rigorous credentialing phase was detailed for all participating centers. One of the stated secondary goals of CREST, to describe this experience in the lead-in phase of CREST, has been completed and published elsewhere.4 Although a 3-year enrollment period was originally anticipated for the main randomized trial, based on 50 sites recruiting 20 symptomatic patients per year, CREST ultimately required nearly 8 …