Zilver PTX Research Articles

Angioscopic Assessment of Early Phase Arterial Repair After Paclitaxel-Coated Nitinol Drug-Eluting Stent Implantation in the Superficial Femoral Artery

Although durable clinical outcomes have been reported, arterial repair after paclitaxel-coated nitinol drug-eluting stent (Zilver PTX) implantation in the superficial femoral artery (SFA) remains unclear. Angioscopic evaluation was performed in SFA intra-stent surfaces 80±29 (range, 49-135) days or 84±18 (range, 52-112) days following Zilver PTX (20 stents in 10 patients; mean age, 72±8 years; 40% men) or bare metal stent (BMS; 14 stents in 9 patients; mean age, 70±7 years; 67% men) implantation, respectively. Neointimal coverage (NIC) was graded as 0, stent struts exposed; grade 1, struts bulging into the lumen, but still transparently visible although covered; grade 2, struts embedded in the neointima, but translucent; grade 3, struts fully embedded and invisible. NIC was defined as heterogeneous when the NIC grade variation was ≥1. Presence of yellow plaque and thrombus were investigated. Dominant NIC was significantly different between Zilver PTX (grade 0, 35%; grade 1, 20%; grade 2, 25%; grade 3, 20%) and BMS (grade 0, 7%; grade 1, 0%; grade 2, 14%; grade 3, 79%; P=0.001). NIC heterogeneity was less frequently observed in Zilver PTX (40% vs. 86%, P=0.009). Prevalence of yellow plaque or thrombus (75% vs. 79%, P=0.57) or thrombus (75% vs. 79%, P=0.57) were similar between Zilver PTX and BMS. Early phase arterial repair was different between Zilver PTX and BMS.

A Budget Impact Model for Paclitaxel-eluting Stent in Femoropopliteal Disease in France

PurposeThe Zilver PTX drug-eluting stent (Cook Ireland Ltd., Limerick, Ireland) represents an advance in endovascular treatments for atherosclerotic superficial femoral artery (SFA) disease. Clinical data demonstrate improved clinical outcomes compared to bare-metal stents (BMS). This analysis assessed the likely impact on the French public health care budget of introducing reimbursement for the Zilver PTX stent.MethodsA model was developed in Microsoft Excel to estimate the impact of a progressive transition from BMS to Zilver PTX over a 5-year horizon. The number of patients undergoing SFA stenting was estimated on the basis of hospital episode data. The analysis from the payer perspective used French reimbursement tariffs. Target lesion revascularization (TLR) after primary stent placement was the primary outcome. TLR rates were based on 2-year data from the Zilver PTX single-arm study (6 and 9 %) and BMS rates reported in the literature (average 16 and 22 %) and extrapolated to 5 years. Net budget impact was expressed as the difference in total costs (primary stenting and reinterventions) for a scenario where BMS is progressively replaced by Zilver PTX compared to a scenario of BMS only.ResultsThe model estimated a net cumulative 5-year budget reduction of €6,807,202 for a projected population of 82,316 patients (21,361 receiving Zilver PTX). Base case results were confirmed in sensitivity analyses.ConclusionAdoption of Zilver PTX could lead to important savings for the French public health care payer. Despite higher initial reimbursement for the Zilver PTX stent, fewer expected SFA reinterventions after the primary stenting procedure result in net savings.

Overview of the 2011 food and drug administration's circulatory system devices panel of the medical devices advisory committee meeting on the Zilver® PTX® Drug-Eluting peripheral stent

Zilver® PTX® (Cook Medical, Bloomington, IN) is a self-expanding nitinol drug-eluting stent with a polymer-free paclitaxel coating on its outer surface. The stent aims to provide improved treatment for patients with symptomatic peripheral arterial disease in the above-the-knee femoropopliteal arteries. On October 13, 2011, the Food and Drug Administration's (FDA) Circulatory System Devices Panel reviewed the Zilver PTX premarket approval application. This summary aims to describe the discussions and recommendations made during the meeting. Based on the Panel's recommendations, it is anticipated that the device will be approved by the FDA.

Nitinol Stents With Polymer-Free Paclitaxel Coating for Lesions in the Superficial Femoral and Popliteal Arteries Above the Knee:Twelve-Month Safety and Effectiveness Results From the Zilver PTX Single-Arm Clinical Study

To report a prospective, single-arm, multicenter clinical study evaluating the Zilver PTX drug-eluting stent for treating the above-the-knee femoropopliteal segment (NCT01094678; http://www.clinicaltrials.gov ). The Zilver PTX drug-eluting stent is a self-expanding nitinol stent with a polymer-free paclitaxel coating. Patients with symptomatic (Rutherford category 2-6) de novo or restenotic lesions (including in-stent stenosis) of the above-the-knee femoropopliteal segment were eligible for enrollment. Between April 2006 and June 2008, 787 patients (578 men; mean age 66.6±9.5 years) were enrolled at 30 international sites. Nine hundred lesions (24.3% restenotic lesions of which 59.4% were in-stent stenoses) were treated with 1722 Zilver PTX stents; the mean lesion length was 99.5±82.1 mm. The 12-month Kaplan-Meier estimates included an 89.0% event-free survival rate, an 86.2% primary patency rate, and a 90.5% rate of freedom from target lesion revascularization. There were no paclitaxel-related adverse events reported. The 12-month stent fracture rate was 1.5%. The ankle-brachial index, Rutherford score, and walking distance/speed scores significantly improved (p<0.001) from baseline to 12 months. These results indicate that the Zilver PTX drug-eluting stent is safe for treatment of patients with de novo and restenotic lesions of the above-the-knee femoropopliteal segment. At 1 year, the overall anatomical and clinical effectiveness results suggest that this stent is a promising endovascular therapy.

Late breaking clinical trials 1

Background: The Zilver® PTX® stent with polymer-free paclitaxel coating is the first drug-eluting stent approved (currently CE marked, investigational in the United States and Japan) for the superficial femoral artery (SFA). This multicenter, multinational, prospective, randomized trial compared the safety and effectiveness of the Zilver PTX study to balloon angioplasty (PTA) and bare metal stenting (BMS). Methods: Symptomatic patients with SFA lesions (de novo or non-instent restenosis) were randomized to PTA or Zilver PTX stent placement. PTA patients experiencing acute failure (e.g. 30% residual stenosis) underwent secondary randomization to provisional stenting with Zilver BMS or Zilver PTX. Follow-up included event-free survival (EFS), and primary patency by Duplex ultrasound core laboratory analysis (peak systolic velocity ratio 2.0). Results: 479 patients were enrolled at 55 institutions in the United States, Japan and Germany, with 241 patients randomized to the Zilver PTX group and 238 to the PTA group. Demographics and lesion characteristics (e.g., lesion length 66 mm and 63 mm, respectively) were similar for the groups. Approximately half the PTA group experienced acute failure and underwent secondary randomization; 59 and 61 patients were assigned to provisional stenting with Zilver BMS and Zilver PTX, respectively. The study results met the 12-month primary endpoint goals showing non-inferior EFS (90.4% versus 82.6%, p 0.01) and superior primary patency (83.1% and 32.8%, p 0.01) for the Zilver PTX compared to PTA. The randomized comparison of provisional stenting with Zilver PTX versus Zilver BMS also showed significant paclitaxel coating benefit, with 12-month patency rates of 89.9% and 73.0% respectively (p 0.01). Currently, 24-month follow-up is available for 278 patients, showing an 86.6% EFS rate and a 74.8% patency rate. The randomized comparison of provisional stenting with Zilver PTX versus Zilver BMS continues to demonstrate significant paclitaxel coating benefit at 24 months, with patency rates of 81.2% and 62.7% respectively (p 0.01). Conclusion: The results of this randomized, multicenter study support the safety and effectiveness of the Zilver PTX Drug-Eluting Peripheral Stent.

AS-001 Zilver PTX Randomized Trial of Paclitaxel-Eluting Stents for Femoropopliteal Artery Disease: 24-Month Update

The Zilver® PTX® stent with polymer-free paclitaxel coating is the first drug-eluting stent approved (currently CE marked, investigational in the United States and Japan) for the superficial femoral artery (SFA). This multicenter, multinational, prospective, randomized trial compared the safety and effectiveness of the Zilver PTX study to balloon angioplasty (PTA) and bare metal stenting (BMS).

Polymer-free Paclitaxel-coated Zilver PTX Stents—Evaluation of Pharmacokinetics and Comparative Safety in Porcine Arteries

Purpose To evaluate the pharmacokinetics and safety of the Zilver PTX Drug-Eluting Stent (Cook Medical, Bloomington, Indiana) in a normal porcine artery model. Materials and Methods Pharmacokinetic analyses were performed using 18 pigs, each implanted with four paclitaxel-coated stents. Paclitaxel remaining on the stents, delivered locally (to artery wall), regionally (to adjacent and downstream muscle), and systemically (to plasma), was determined at various times through 56 days. For safety evaluation, local, regional, and systemic responses were grossly and histologically assessed at 1 month, 3 months, and 6 months in 21 additional pigs and compared with the responses to bare metal stents in 21 separate pigs. Results Stents delivered approximately 95% of the total paclitaxel within 24 hours after deployment. Nonetheless, there were sustained paclitaxel levels in the artery wall through 56 days, maintained at approximately 20% of the peak level through 14 days. Very little paclitaxel was distributed regionally or systemically, becoming undetectable in plasma at 10 hours. Complete necropsy, hematology, and serum chemistry revealed no adverse effects associated with the paclitaxel-coated stents. Within 3 months, vessels with both paclitaxel-coated and bare metal stents showed comparable, complete healing. Conclusions The Zilver PTX stent appears to be safe, achieves sustained paclitaxel levels in the artery wall, and shows complete vessel healing comparable to bare metal stents within 3 months.

Abstract No. 7: Prospective randomised controlled trial comparing drug eluting stent (DES) versus percutaneous transluminal angioplasty (PTA) for the treatment of hemodialysis arterio-venous graft (AVG) stenoses: Preliminary report

To compare the effectiveness and safety of the Zilver PTX Drug Eluting Stent (DES) versus conventional percutaneous transluminal angioplasty (PTA) in maintaining patency of the venous graft anastomotic stenosis in patients with dysfunctional hemodialysis arterio-venous graft (AVG).

Evolving Modalities for Femoropopliteal Interventions

Despite technical advances in balloon design and technique, there has been little improvement of primary patency rates after balloon-based endovascular interventions for all but focal femoropopliteal lesions. Improving on stainless steel models, nitinol stents have been associated with favorable short- and midterm primary patency rates; studies with longer-term follow-up will be required to learn whether restenosis is ongoing, with continued loss of primary patency. Studies in recent years have shown varying incidences of mechanical fatigue leading to nitinol stent fracture. Covered stents are designed to prevent the tissue infiltration and intimal hyperplasia that can lead to bare metal in-stent restenosis. Several clinical studies, mainly single-center registries, have demonstrated a general effectiveness of the Hemobahn/Viabahn polytetrafluoroethylene-covered stent-grafts, approved for femoral arterial occlusive disease, and have helped to distinguish indications for use and to delineate possible failure modes. A multicenter randomized trial, which has completed enrollment, will compare the Viabahn with self-expanding bare nitinol stents. The primary use of drug-eluting stents (DES) has become routine clinical practice for coronary artery disease. The 2-phase multicenter randomized double-blind SIROCCO trials have been completed, with results published through 24 months. Follow-up demonstrated the feasibility and safety of deploying sirolimus-eluting stents in the femoropopliteal segment but failed to show superior efficacy for DES versus bare nitinol stents. However, the restenosis rates with bare metal stents were unexpectedly low. A paclitaxel-eluting stent without a polymer coating is currently being evaluated in the recently enrolled Zilver PTX randomized trial and international registry. A polymer-based everolimus-eluting stent is being evaluated for femoropopliteal use in the nonrandomized European STRIDES trial. Balloons coated with paclitaxel have recently been evaluated for simple femoropopliteal disease with encouraging results through 2 years of follow-up. The bioabsorbable stent concept emerged in response to the potential issues with metal stents, but to date no investigational device has successfully overcome issues such as relatively low radial force and variable degradation rates.

Cook Medical's paclitaxel-eluting peripheral stent [Zilver PTX] has performed well,

Cook Medical's paclitaxel-eluting peripheral stent [Zilver PTX] has performed well,

Superoxide dismutase in development of obliterative bronchiolitis

Although clinical trials demonstrated the superiority of the Zilver (Cook Medical, Bloomington, Ind) paclitaxel-eluting stent (PTX), a recently developed drug-eluting stent (DES), to conventional therapy for femoropopliteal (FP) lesions, the incidence and risk factors of the repetition of reintervention after DES implantation in clinical practice remained unrevealed.This was a subanalysis of the ZEPHYR (ZilvEr PTX for tHe Femoral ArterY and Proximal Popliteal ArteRy) study, enrolling FP lesions undergoing endovascular therapy (EVT) with DES implantation. The current study analyzed the 2-year database including 583 FP lesions in 495 patients undergoing preoperative intravascular ultrasound imaging before DES implantation. The primary outcome measure was re-re-EVT, defined as undergoing additional EVT more than once during the 2-year follow-up after DES implantation. The secondary outcome measure was re-EVT, defined as undergoing at least one additional EVT during the follow-up.Critical limb ischemia (CLI) was present in 28% of the study population, 23% had a history of EVT, and 43% had chronic total occlusion. Mean lesion length was 16 ± 10 cm, and intravascular ultrasound imaging-evaluated external elastic membrane area was 28 ± 10 mm2. The cumulative incidence rate of re-re-EVT at 2 years was estimated to be 14%, whereas that of re-EVT was 31%. After multivariate analysis, CLI and smaller external elastic membrane area were independently associated with the outcome.The incidence and risk factors of the repetition of reintervention after DES implantation for FP lesions were revealed. The current findings suggest that DES implantation might be a careful indication in CLI cases especially with a small vessel.