Polymer-based drug-eluting stent treatment extends the time to reintervention for patients with symptomatic femoropopliteal artery disease: clinical evidence and potential economic value.

Aim: Use long-term follow-up data from the IMPERIAL study to determine whether drug-eluting polymer-based nitinol stent treatment can delay the time to repeat intervention for femoropopliteal artery disease and how such a delay may result in cost savings in a value-based episode of care. Patients & methods: The IMPERIAL randomized controlled trial was an international study of a paclitaxel-eluting polymer-coated stent (Eluvia, Boston Scientific, MA, USA) versus a polymer-free paclitaxel-coated stent (Zilver PTX, Cook Corporation, IN, USA) for treating lesions of the femoropopliteal arterial segment. Study patients (n = 465) had symptomatic lower limb ischemia. Safety and efficacy assessments were performed through 5 years. Mean time to first reintervention was calculated in post-hoc analysis for patients who underwent a clinically driven target lesion revascularization (CD-TLR) through 3 or 5 years following the index procedure. To simulate potential cost savings associated with differential CD-TLR burden over time, a cost-avoidance analysis using input parameters from IMPERIAL and US 100% Medicare standard analytical files was developed. Results: Among patients with a first CD-TLR through 3 years of follow-up, mean time to reintervention was 5.5 months longer (difference 166 days, 95% CI: 51, 282 days; p = 0.0058) for patients treated with Eluvia (n = 56) than for those treated with Zilver PTX (n = 30). Through the 5-year study follow-up period, CD-TLR rates were 29.3% (68/232) for Eluvia and 34.2% (39/114) for Zilver PTX (p = 0.3540) and mean time to first reintervention exceeded 2 years for patients treated with Eluvia at 737 days versus 645 days for the Zilver PTX group (difference 92 days, 95% CI: -85, 269 days; p = 0.3099). Simulated savings considering reinterventions occurring over 1 and 5 years following initial use of Eluvia over Zilver PTX were US $1,395,635 and US $1,531,795, respectively, when IMPERIAL CD-TLR rates were extrapolated to 1000 patients. Conclusion: IMPERIAL data suggest initial treatment with Eluvia extends the time patients spend without undergoing reintervention. This extension may be associated with cost savings in relevant time frames.

Why selective screening for asymptomatic carotid stenosis is currently appropriate: a special report.

INTRODUCTION: Two of the main reasons recent guidelines do not recommend routine population-wide screening programs for asymptomatic carotid artery stenosis (AsxCS) is that screening could lead to an increase of carotid revascularization procedures and that such mass screening programs may not be cost-effective. Nevertheless, selective screening for AsxCS could have several benefits. This article presents the rationale for such a program. AREAS COVERED: The benefits of selective screening for AsxCS include early recognition of AsxCS allowing timely initiation of preventive measures to reduce future myocardial infarction (MI), stroke, cardiac death and cardiovascular (CV) event rates. EXPERT OPINION: Mass screening programs for AsxCS are neither clinically effective nor cost-effective. Nevertheless, targeted screening of populations at high risk for AsxCS provides an opportunity to identify these individuals earlier rather than later and to initiate a number of lifestyle measures, risk factor modifications, and intensive medical therapy in order to prevent future strokes and CV events. For patients at 'higher risk of stroke' on best medical treatment, a prophylactic carotid intervention may be considered.

Recent advances and controversial issues in the optimal management of asymptomatic carotid stenosis.

OBJECTIVE: The optimal management of patients with asymptomatic carotid stenosis (AsxCS) is enduringly controversial. We updated our 2021 Expert Review and Position Statement, focusing on recent advances in the diagnosis and management of patients with AsxCS. METHODS: A systematic review of the literature was performed up to August 1, 2023, using PubMed/PubMed Central, EMBASE and Scopus. The following keywords were used in various combinations: "asymptomatic carotid stenosis," "carotid endarterectomy" (CEA), "carotid artery stenting" (CAS), and "transcarotid artery revascularization" (TCAR). Areas covered included (i) improvements in best medical treatment (BMT) for patients with AsxCS and declining stroke risk, (ii) technological advances in surgical/endovascular skills/techniques and outcomes, (iii) risk factors, clinical/imaging characteristics and risk prediction models for the identification of high-risk AsxCS patient subgroups, and (iv) the association between cognitive dysfunction and AsxCS. RESULTS: BMT is essential for all patients with AsxCS, regardless of whether they will eventually be offered CEA, CAS, or TCAR. Specific patient subgroups at high risk for stroke despite BMT should be considered for a carotid revascularization procedure. These patients include those with severe (≥80%) AsxCS, transcranial Doppler-detected microemboli, plaque echolucency on Duplex ultrasound examination, silent infarcts on brain computed tomography or magnetic resonance angiography scans, decreased cerebrovascular reserve, increased size of juxtaluminal hypoechoic area, AsxCS progression, carotid plaque ulceration, and intraplaque hemorrhage. Treatment of patients with AsxCS should be individualized, taking into consideration individual patient preferences and needs, clinical and imaging characteristics, and cultural, ethnic, and social factors. Solid evidence supporting or refuting an association between AsxCS and cognitive dysfunction is lacking. CONCLUSIONS: The optimal management of patients with AsxCS should include BMT for all individuals and a prophylactic carotid revascularization procedure (CEA, CAS, or TCAR) for some asymptomatic patient subgroups, additionally taking into consideration individual patient needs and preference, clinical and imaging characteristics, social and cultural factors, and the available stroke risk prediction models. Future studies should investigate the association between AsxCS with cognitive function and the role of carotid revascularization procedures in the progression or reversal of cognitive dysfunction.

Carotid Artery Stenting: JACC State-of-the-Art Review.

Significant advances in the field of carotid artery stenting (CAS) have occurred, including new randomized trial data, recent professional societal statements for competency, new techniques and new devices that have been developed, and perhaps most importantly, our understanding of how to better select candidates for CAS to avoid periprocedural complications. The current Centers for Medicare and Medicaid Services coverage decision regarding CAS is outdated, and our review supports our recommendation to approve CAS in selected candidates who are symptomatic with a carotid stenosis ≥50% and ≤99% and for asymptomatic patients with carotid stenosis ≥70% and ≤99% for stroke prevention. Optimized CAS strategies have allowed experienced operators to better assess procedure risk before CAS and have led to continued improvement in CAS outcomes. New technologies including enhanced embolic protection devices and dual-layered stents should result in further improvement.

Cost-effectiveness of a paclitaxel-eluting stent (Eluvia) compared to Zilver PTX for endovascular femoropopliteal intervention.

OBJECTIVES: Antiproliferative therapies based on paclitaxel have been developed to extend the durability of endovascular interventions for lower-extremity atherosclerotic peripheral artery disease, resulting in improved primary vessel patency and fewer target lesion revascularizations. This study evaluated the cost-effectiveness of the sustained-release, paclitaxel-eluting Eluvia stent (Boston Scientific, Marlborough, MA) versus the paclitaxel-coated Zilver PTX stent (Cook Medical, Bloomington, IN) for endovascular intervention in the superficial femoral or proximal popliteal artery. DESIGN: A microsimulation model was constructed from a United States Medicare perspective with a 24-month time horizon. Patients entering the model were assigned to initial endovascular intervention with either Eluvia or Zilver PTX. Each month patients were exposed to the risks of primary vessel patency loss, target lesion revascularization, amputation, and death. Clinical input parameters were taken from a randomized trial (IMPERIAL) comparing the two interventions at 24-months follow-up. Cost parameters were obtained from analyses of Medicare administrative and claims data. Cost-effectiveness analysis entailed sampling a complete set of clinical and cost parameters from their respective distributions, and then running cohorts of 10,000 patients through each intervention arm of the model. One-way and probabilistic sensitivity analyses were performed. RESULTS: In the base case microsimulation, at 24 months, the modeled target lesion revascularization was 11.6% for Eluvia and 19.0% for Zilver PTX, and the mean total direct costs were $20,010 and $21,356, respectively (Eluvia average savings=$1,346). In probabilistic sensitivity analyses, Eluvia was cost-effective in 87.8% of all simulations at a willingness-to-pay threshold of $10,000 per target lesion revascularization prevented. Eluvia was more effective and less costly (dominant) than Zilver PTX in 73.6% of simulations. CONCLUSIONS: In this comparison of a paclitaxel-eluting to a paclitaxel-coated stent for endovascular femoropopliteal intervention, Eluvia was more effective and less costly (dominant) than Zilver PTX from a US Medicare perspective. These findings should be considered when formulating reimbursement policy and clinical practice guidelines.

Paclitaxel is a drug used in the treatment of peripheral artery disease (PAD) to help maintain primary vessel patency and reduce the need for revascularization procedures. This study evaluated the cost-effectiveness of the paclitaxel-eluting Eluvia stent (Boston Scientific, Marlborough, MA) versus the paclitaxel-coated Zilver PTX stent (Cook Medical, Bloomington, IN) in Medicare patients with PAD. Cost-effectiveness is defined as the degree to which a particular treatment option is effective relative to its costs. Therefore, this study compared both the effectiveness, in terms of target lesion revascularization rates, and the costs of Eluvia versus Zilver PTX over 24 months.A microsimulation model was developed from a United States Medicare perspective with a 24-month time horizon. Simulated patients entered the model and were assigned to receive either Eluvia or Zilver PTX. Monthly, patients were exposed to the risks of primary vessel patency loss, target lesion revascularization (TLR), amputation, and death. These risks were taken from a randomized controlled trial that compared Eluvia and Zilver PTX over 24 months. Patients also accrued costs over time. The costs used in the model were obtained from Medicare administrative and claims data analyses.In health economics, a treatment is considered to be the dominant treatment option if it is both more effective and less costly than the alternative treatment. In this case, Eluvia was found to be dominant over Zilver PTX because it was associated with lower TLR rates and lower costs. These findings should be considered when formulating reimbursement policy and clinical practice guidelines.

Preclinical Assessment of a Novel Conformable Foam-Based Left Atrial Appendage Closure Device.

BACKGROUND: Left atrial appendage (LAA) occlusion has been established as an alternative to systemic anticoagulation for stroke prevention in patients with atrial fibrillation; however, limitations of current devices have slowed adoption. We present preclinical evaluations of a novel device, the Conformal Left Atrial Appendage Seal (CLAAS). METHODS: An in vitro assessment of conformability was conducted to evaluate the two CLAAS devices (regular 27 mm and large 35 mm) and a Watchman 2.5 (27 mm). Devices were placed within silicone tubes and compressed in a vise submerged in a water bath at 37°C. Changes in device diameter and visual seal were noted. Acute (n = 1) and chronic 60-day (n = 6) canine studies with gross and histologic assessment were performed. RESULTS: Conformability bench tests demonstrated that the regular CLAAS implant was able to seal oval orifices from 20 × 30 mm to 15 × 33 mm and the large from 30 × 35 mm to 20 × 40 mm. As the CLAAS implant was compressed in the minor diameter, it increased in the major diameter, thereby filling the oval space, whereas the Watchman 2.5 showed gaps and maintained its round configuration when compressed in one direction. Seven devices were successfully implanted in the canine model with complete seal without thrombus. Histologic examination showed complete neointima covering with minimal inflammation at 60 days. CONCLUSIONS: Preclinical testing demonstrated the conformability of the CLAAS implant and its ability to seal the LAA. Clinical studies are ongoing to characterize the utility of the CLAAS implant in the treatment of patients with atrial fibrillation.

Peripheral vascular disease in women: Are we analyzing the costs correctly?

Women treated with a peripheral vascular intervention, on average, have more comorbidities and cost more per hospital admission than women treated with a percutaneous coronary intervention. The impact of critical limb ischemia on these results is likely significant, but not available in these data. Physicians need to be more aware of the differences in the risks and manifestations of cardiovascular disease in women.

Mortality Assessment of Paclitaxel-Coated Balloons: Patient-Level Meta-Analysis of the ILLUMENATE Clinical Program at 3 Years.

BACKGROUND: A recent summary-level meta-analysis comprising randomized, controlled trials (RCTs) of femoropopliteal paclitaxel-coated balloon and stent intervention identified excess late mortality in the paclitaxel-treated patients. METHODS: We evaluated the safety of the Stellarex drug-coated balloon (DCB) for femoropopliteal artery disease with an independently performed meta-analysis of patient-level data from all patients in the Stellarex femoropopliteal clinical program. To compare mortality after DCB or uncoated percutaneous transluminal angioplasty (PTA), we aggregated data from 2 RCTs comprising 419 patients treated with DCB and 170 patients treated with PTA. In an additional analysis, data were aggregated from 6 poolable Stellarex DCB studies (2 RCTs, 3 single-arm studies, and 1 registry). All serious adverse events including deaths were adjudicated by a blinded, third-party, independent Clinical Events Committee. Kaplan-Meier estimates in the RCTs were compared with restricted mean survival time. Predictors of death were assessed with hazard ratios (HRs) and Cox proportional hazards modeling. RESULTS: Baseline characteristics were similar in the patients treated with DCB and PTA in the pooled RCT analysis, with the exception that the DCB cohort was younger (67.4±9.7 versus 69.4±9.4 years, P=0.02), smoked more frequently (86.6% versus 78.8%, P=0.02), and were less often treated for recurrent lesions (8.8% versus 14.7%, P=0.04). In the RCTs, patients treated with DCB had all-cause mortality rates that were not different from those of patients treated with PTA (Kaplan-Meier estimates 1.8±0.7% versus 1.3±0.9%, 6.5±1.2% versus 5.9±1.9%, and 9.3±1.5% versus 9.9±2.4% at 1, 2, and 3 years, respectively, P=0.86). All-cause mortality rates were similar in a 1906-patient pooled nonrandomized DCB data set (Kaplan-Meier estimates of 2.1%, 4.9%, and 7.0% at 1, 2, and 3 years, respectively). Clinical Events Committee-adjudicated causes of death were balanced between the DCB and PTA cohorts. Multivariable Cox modeling identified age (HR, 1.06; 95% CI, 1.04-1.08; P<0.001), diabetes mellitus (HR, 1.42; 95% CI, 1.01-2.00; P=0.04), congestive heart failure (HR, 1.88; 95% CI, 1.12-3.16; P=0.02), and renal insufficiency (HR, 2.00; 95% CI, 1.33-3.01; P<0.001) as predictors of mortality. Paclitaxel exposure was unrelated to mortality (HR, 1.04; 95% CI, 0.98-1.10; P=0.23). CONCLUSIONS: The mortality rates for patients treated with the DCB and uncoated PTA were indistinguishable over 3-year follow-up. Additional patient-level, adequately powered meta-analyses with larger RCT data sets will be needed to confirm the generalizability of these findings. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02110524, NCT01858363, NCT01858428, NCT03421561, NCT01912937, NCT01927068, and NCT02769273.

The impact of regulatory approval and Medicare coverage on outcomes of carotid stenting.

BACKGROUND: Carotid artery stenting (CAS) was introduced in the United States nearly a decade ago as a novel treatment of severe carotid stenosis. Voluminous and high-quality prospective data permit analysis of longitudinal trends in CAS outcomes. METHODS: Outcomes from all prospective trials with the Food and Drug Administration (FDA) oversight from 2000-2011 were reviewed, as were the subset of studies using a single CAS system. All studies shared common inclusion/exclusion criteria, endpoints, independent assessment/adjudication of neurological events, and were conducted in accordance with FDA regulations. Death and stroke (DS) rates from FDA-approved studies in high-surgical-risk patients were assessed. RESULTS: Between 2000 and 2011, two distinct periods with clustered and differentiated outcomes in CAS IDE trials were observed, separated by FDA approval and Centers for Medicare and Medicaid Services (CMS) coverage in 2004-2005. The mean 30-day DS rate in the first wave (2000-2004) of CAS trials was 5.3% (95% CI: 4.6-6.2%), and fell significantly to 2.6% (95% CI: 1.9-3.7%; P = 0.0001) in the second wave (2006-2011). This decline occurred during a simultaneous, independent 24-fold increase in monitored CAS activity. This decline in DS rates was observed in symptomatic and asymptomatic patients, alike independent of device tested. CONCLUSIONS: Declines in periprocedural DS rates in CAS appear linked to regulatory and coverage approvals leading to increased operator experience along with continued regulatory oversight, and provide insight into the introduction of other novel therapies.

Objective simulator-based evaluation of carotid artery stenting proficiency (from Assessment of Operator Performance by the Carotid Stenting Simulator Study [ASSESS]).

Studies have suggested that operator proficiency has a substantial effect on complication rates and procedural outcomes. Endovascular simulators have been used for training and have been proposed as an alternative to the conventional assessment of skills. The present study sought to validate simulation as an objective method for proficiency evaluation in carotid artery stenting. Interventional cardiologists classified as novice, intermediate, or experienced practitioners performed 3 simulated, interactive carotid stenting cases on an AngioMentor endovascular simulator. An automated algorithm scored the participants according to the technical performance, medical management, and angiographic results. A total of 33 interventional cardiologists (8 novices, 15 intermediates, and 10 experts) completed 82 simulated procedures. The composite scores for the case simulations varied significantly by operator experience, with better scores for the more experienced groups (p <0.0001). The metrics that discriminated between operator experience groups included fluoroscopy time, crossing the carotid lesion with devices other than a 0.014-in. wire before filter deployment, and incomplete coverage of the lesion by the stent. In conclusion, the results of the present study validate that a simulator with an automated scoring system is able to discriminate between levels of operator proficiency for carotid artery stenting. Simulator-based performance assessment could have a role in initial and ongoing proficiency evaluations and credentialing of interventional operators of high-risk endovascular procedures.

Costs and cost-effectiveness of carotid stenting versus endarterectomy for patients at standard surgical risk: results from the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST).

BACKGROUND AND PURPOSE: The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) demonstrated similar rates of the primary composite end point between carotid artery stenting (CAS) and carotid endarterectomy (CEA), although the risk of stroke was higher with CAS, and the risk of myocardial infarction was higher with CEA. Given the large number of patients who are candidates for these procedures, an understanding of their relative cost and cost-effectiveness may have important implications for health care policy and treatment guidelines. METHODS: We performed a formal economic evaluation alongside the CREST trial. Costs were estimated from all trial participants over the first year of follow-up using a combination of resource use data and hospital billing data. Patient-level health use scores were obtained using data from the SF-36. We then used a Markov disease-simulation model calibrated to the CREST results to project 10-year costs and quality-adjusted life expectancy for the 2 treatment groups. RESULTS: Although initial procedural costs were $1025/patient higher with CAS, postprocedure costs and physician costs were lower such that total costs for the index hospitalization were similar for the CAS and CEA groups ($15 055 versus $14 816; mean difference, $239/patient; 95% CI for difference, -$297 to $775). Neither follow-up costs after discharge nor total 1-year costs differed significantly. For the CREST population, model-based projections over a 10-year time horizon demonstrated that CAS would result in a mean incremental cost of $524/patient and a reduction in quality-adjusted life expectancy of 0.008 years compared with CEA. Probabilistic sensitivity analysis demonstrated that CEA was economically attractive at an incremental cost-effectiveness threshold of $50 000/quality-adjusted life-year gained in 54% of samples, whereas CAS was economically attractive in 46%. CONCLUSIONS: Despite slightly lower in-trial costs and lower rates of stroke with CEA compared with CAS, projected 10-year outcomes from this controlled clinical trial demonstrate only trivial differences in overall healthcare costs and quality-adjusted life expectancy between the 2 strategies. If the CREST results can be replicated in clinical practice, these findings suggest that factors other than cost-effectiveness should be considered when deciding between treatment options for carotid artery stenosis in patients at standard risk for surgical complications. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique Identifier: NCT00004732.

Costs and cost-effectiveness of carotid stenting versus endarterectomy for patients at increased surgical risk: results from the SAPPHIRE trial.

OBJECTIVES: To evaluate the cost-effectiveness of carotid stenting vs. carotid endarterectomy using data from the SAPPHIRE trial. BACKGROUND: Carotid stenting with embolic protection has been introduced as an alternative to carotid endarterectomy for prevention of cerebrovascular and cardiovascular events among patients at increased surgical risk. METHODS: Between August 2000 and July 2002, 310 patients with an accepted indication for carotid endarterectomy but at high risk of complications were randomized to and subsequently underwent either carotid stenting (n = 159) or endarterectomy (n = 151). Clinical outcomes, resource use, costs, and quality of life were assessed prospectively for all patients over a 1-year period. Life expectancy, quality-adjusted life expectancy, and health care costs beyond the follow-up period were estimated for patients alive at 1 year, based on observed clinical events during the first year of follow-up. RESULTS: Although initial procedural costs were significantly higher for stenting than for endarterectomy (mean difference: $4,081/patient; 95% CI, $3,849-$4,355), mean post-procedure length of stay was shorter for stenting (1.9 vs. 2.9 days; P < 0.001) with significant associated cost offsets. As a result, initial hospital costs were just $559/patient higher with stenting (95% CI, $3,470 less to $2,289 more). Neither follow-up costs after discharge nor total 1-year costs differed significantly. The incremental cost-effectiveness ratio for stenting compared with endarterectomy was $6,555 per quality-adjusted life year (QALY) gained, with over 98 percent of bootstrap estimates < $50,000/QALY gained. CONCLUSIONS: Although carotid stenting with embolic protection is more costly than carotid endarterectomy, by commonly accepted standards, stenting is an economically attractive alternative to endarterectomy for patients at high surgical risk.

Echocardiographic guidance and assessment of percutaneous repair for mitral regurgitation with the Evalve MitraClip: lessons learned from EVEREST I.

OBJECTIVE: Percutaneous mitral repair is rapidly developing as an alternative to cardiac surgery in select patients. The Evalve percutaneous E2E system uses the MitraClip to replicate the surgical suture-based approach. This procedure requires real-time echocardiographic guidance in a unique and significant collaboration between echocardiographer and interventionalist. transesophageal echocardiography (TEE) is used as the primary imaging modality to guide this procedure and is essential to its success. METHODS: In EVEREST I, the US multicenter phase I safety and feasibility trial, 47 patients with 3 or 4+ mitral regurgitation (MR) were enrolled. The trial involved a standardized echocardiographic imaging protocol with a standardized anatomic-based vocabulary, predetermined standard TEE views, preprocedural strategy meetings, and display of echocardiographic aids to optimize communication and procedural efficiency during placement of the clip. RESULTS: TEE guidance facilitated the creation of a double-orifice mitral valve in all 47 patients enrolled (100%), and 40 patients were discharged with 1 or more clips (85%). At discharge, successful placement of a clip and

Carotid stenting and endarterectomy: a clinical and cost comparison of revascularization strategies.

BACKGROUND AND PURPOSE: Investigational carotid stenting for extracranial carotid stenosis has demonstrated procedural results approaching those reported with endarterectomy, but with limited cost and long-term data. This study compared the in-hospital outcomes and costs of these 2 revascularization strategies at a single institution and the long-term effectiveness of carotid stenting. METHODS: Data for 136 endarterectomies and 136 carotid stent procedures at a tertiary-care community hospital were obtained. The primary clinical outcome measures were in-hospital major ipsilateral stroke and death. In-hospital direct variable costs and length of stay were the primary economic measures. Information on restenosis and late ipsilateral stroke for the stent group was available at 2-year follow-up. RESULTS: These nonrandomized groups were similar, but the endarterectomy group had more symptomatic patients (42% versus 31%; P=0.0004), and the stent group had more NASCET-excluded patients (68% versus 35%; P<0.0001). In-hospital major ipsilateral stroke and death occurred more frequently in the surgical group, but the difference was not significant (2.9% versus 0%; P=0.1). Minor ipsilateral strokes were similar (2.2% versus 2.9%; P=NS). Cost ($5409 versus $3417; P<0.0001) and length of stay (3.0 versus 1.4 days; P<0.0001) were significantly greater for the surgical group. In the stent group, 6-month angiographic restenosis was 3.1%, and 2-year ipsilateral major stroke rate was 0%. CONCLUSIONS: In-hospital outcomes with carotid stenting were similar to those with endarterectomy but were achieved in patients with significantly more comorbidities. Cost and resource utilization with stenting were substantially less than those with endarterectomy. At 2 years, carotid stenting appeared not only durable but also effective in stroke prevention.