Patient-level meta-analysis of 999 claudicants undergoing primary femoropopliteal nitinol stent implantation.

CONDENSED ABSTRACT: The factors that impact the clinical effectiveness of bare nitinol stents in claudicants with symptomatic femoropopliteal atherosclerosis are incompletely known. The authors analyzed variables that may influence stent durability and provide a benchmark for their effectiveness. Data analyzed from six studies (999 patients) included baseline noninvasive hemodynamic tests, angiographic characteristics, ultrasound defined stent patency and target lesion revascularization through 12-months. Baseline ankle-brachial index and lesion length predicted stent patency and target lesion revascularization and when combined interacted significantly to better predict outcomes. This meta-analysis provides an important comparator against which emerging therapies that treat claudicants with femoropopliteal atherosclerosis can be assessed. SUBJECT CODE: Peripheral Artery Disease BACKGROUND: The performance of bare metal nitinol stents in patients with symptomatic femoropopliteal peripheral artery disease (PAD) is not well defined. METHODS: Patient-level data from six large prospective trials sponsored by medical device manufacturers was abstracted and analyzed to identify a cohort of patients with claudication and femoropopliteal artery occlusive disease. Twelve-month binary patency and target lesion revascularization (TLR) rates were primary outcomes. Stent patency was assessed by duplex ultrasonography (DUS) and TLR was a clinically driven intervention. To characterize the effects of patient characteristics on the outcomes, meta-regression was performed via mixed effects logistic regression models with patient-level covariates. RESULTS: About 999 patients were analyzed; the mean ABI was 0.68 ± 0.18, the mean lesion length was 84 ± 53 mm, the mean lesion stenosis was 78%, and nearly two thirds of patients had mild to severe calcification. The mean Rutherford clinical category was 2.7 ± 0.6 and ranged from 2.6 to 2.8 in all studies. The 12-month patency across all studies was 69.8% and TLR rates ranged from 9.2% to 19.7%. Multivariable analysis demonstrated that baseline ABI and baseline target lesion length predicted both primary patency and TLR. Further, these two variables interacted significantly to better predict TLR outcomes when used in combination. CONCLUSION: The 12-month clinical effectiveness of bare nitinol stents to treat patients with symptomatic femoropopliteal PAD is acceptable and is impacted by clinical and lesion-specific characteristics. These data provide an important and useful benchmark to compare the clinical benefit of emerging endovascular PAD therapies. © 2017 Wiley Periodicals, Inc.

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.

PURPOSE: 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 ). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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.

Percutaneous occlusion of the left subclavian and celiac arteries before or during endograft repair of thoracic and thoracoabdominal aortic aneurysms with detachable nitinol vascular plugs.

PURPOSE: To review an experience with the Amplatzer vascular plug (AVP) for prevention of type II endoleaks during endovascular aneurysm repair (EVAR) of thoracic and thoracoabdominal aneurysms. MATERIALS AND METHODS: Retrospective review was undertaken of 14 patients undergoing transcatheter occlusion of the left subclavian (n = 12) or celiac artery (n = 2) with the AVP as part of EVAR of thoracic and thoracoabdominal aneurysms at a single institution. Procedural criteria evaluated were success at target vessel occlusion, the number of AVPs used, use of adjunctive embolization devices, and embolization-related ischemic end-organ events. Follow-up imaging criteria included evaluation of persistent target vessel occlusion, evidence of device migration, and the presence and characterization of endoleak secondary to AVP failure. RESULTS: Complete target vessel occlusion was documented for all cases. In six cases, more than one AVP was placed, with an average of 1.5 devices per patient. In two cases, adjunctive coils were placed. Computed tomographic or magnetic resonance angiography follow-up was available for all patients (mean follow-up, 419 days; range 28-930 d). No case showed evidence of device migration or type II endoleak resulting from AVP failure. There was a single instance of left subclavian artery recanalization without type II endoleak. There were no embolization-related ischemic end-organ events. CONCLUSIONS: Transcatheter arterial occlusion of the subclavian and celiac arteries with the AVP is a valuable adjunct to endografting in cases in which side branch embolization is necessary to extend the landing zone.

Treatment of femoropopliteal in-stent restenosis with paclitaxel-eluting stents.

OBJECTIVES: This study sought to evaluate the outcomes of drug-eluting stent treatment for femoropopliteal in-stent restenosis (ISR). BACKGROUND: ISR after femoropopliteal interventions is an increasing problem. Although the role of drug-eluting stents in the treatment of coronary ISR is well defined, no published studies have examined drug-eluting stents in the treatment of femoropopliteal ISR. METHODS: This study examines 108 patients with 119 ISR lesions who were enrolled in the ZILVER-PTX single-arm study, a prospective, multicenter clinical trial of 787 patients. All patients were treated with paclitaxel-eluting nitinol stents. RESULTS: Mean patient age was 68.3 ± 9.4 years; 61.1% of patients were men. Mean lesion length was 133.0 ± 91.7 mm; 33.6% of lesions were >150 mm long and 31.1% of lesions were totally occluded. Procedural success was achieved in 98.2% of lesions with 2.1 ± 1.2 stents placed per lesion. Primary patency was 95.7% at 6 months and 78.8% at 1 year. Freedom from target lesion revascularization was 96.2% at 6 months, 81.0% at 1 year, and 60.8% at 2 years. Forty patients experienced major adverse events, exclusively target lesion revascularization. Before treatment, 81.1% of patients had Rutherford scores ≥3; at 2 years, 60.9% of patients had Rutherford scores ≤1. Both ankle brachial index and walking impairment questionnaire scores significantly improved following treatment. The 1-year fracture rate of stents used in ISR lesions was 1.2%. No significant risk factors associated with loss of patency were identified. CONCLUSIONS: Treatment of femoropopliteal ISR with paclitaxel-eluting stents results in favorable acute, midterm, and long-term outcomes. (Zilver PTX Global Registry [ZILVER-PTX]; NCT01094678).

Infolding and collapse of thoracic endoprostheses: manifestations and treatment options.

OBJECTIVES: We sought to review the clinical sequelae and imaging manifestations of thoracic aortic endograft collapses and infoldings and to evaluate minimally invasive methods of repairing such collapses. METHODS: Two hundred twenty-one Gore endografts (Excluder, TAG; W. L. Gore & Associates, Inc, Flagstaff, Ariz) were deployed in 145 patients for treatment of pathologies including aneurysms and pseudoaneurysms, dissections, penetrating ulcers, transections, fistulae, mycotic aneurysms, and neoplastic invasions in 6 different prospective trials at a single institution from 1997 to 2007. Device collapses and infoldings were analyzed retrospectively, including review of anatomic parameters, pathologies treated, device sizing and selection, clinical sequelae, methods of repair, and outcome. RESULTS: Six device collapses and infoldings were identified. Oversized devices placed into small-diameter aortas and imperfect proximal apposition to the lesser curvature were seen in all proximal collapses, affecting patients with transections and pseudoaneurysms. Infoldings in patients undergoing dissection represented incomplete initial expansion rather than delayed collapse. Delayed collapse occurred as many as 6 years after initial successful deployment, apparently as a result of changes in the aortic configuration from aneurysmal shrinkage. Clinical manifestations ranged from life-threatening ischemia to complete lack of symptoms. Collapses requiring therapy were remedied percutaneously by bare stenting or in one case by branch vessel embolization. CONCLUSIONS: Use of oversized devices in small aortas carries a risk of device failure by collapse, which can occur immediately or after years of delay. When clinically indicated, percutaneous repair can be effectively performed.

Randomized, multicenter study comparing expanded polytetrafluoroethylene-covered endoprosthesis placement with percutaneous transluminal angioplasty in the treatment of superficial femoral artery occlusive disease.

PURPOSE: To compare the safety and effectiveness of the Viabahn endoprosthesis with that of percutaneous transluminal angioplasty (PTA) alone in the treatment of symptomatic peripheral arterial disease (PAD) affecting the superficial femoral artery (SFA). MATERIALS AND METHODS: From 1998 to 1999, patients with symptomatic SFA PAD were enrolled in a prospective, multicenter randomized study and underwent either PTA alone (n = 100) or PTA followed by stent-graft placement (expanded polytetrafluoroethylene/nitinol self-expanding stent-graft) (n = 97) for stenoses or occlusions of the SFA that were 13 cm long or shorter. At baseline, there were no significant differences between the PTA and stent-graft treatment groups, including chronic limb ischemia status and treated lesion length. RESULTS: The stent-graft group had a significantly higher technical success rate (95% vs 66%, P < .0001) and 1-year primary vessel patency rate at duplex ultrasonography (65% vs 40%, P = .0003). A patency benefit was seen for lesions at least 3 cm long. At 12 months, chronic limb ischemia status was 15% further improved for the stent-graft group (P = .003). There were no significant differences between treatment groups with regard to the occurrence of early or late major adverse events. CONCLUSIONS: In this multicenter study, the patency, technical success, and clinical status results obtained with stent-grafts were superior to those obtained with PTA alone.

MR-guided transjugular intrahepatic portosystemic shunt creation with use of a hybrid radiography/MR system.

PURPOSE: To evaluate the performance of a combined hybrid radiography/magnetic resonance (MR) unit to guide portal vein (PV) puncture during human transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS: Fourteen patients undergoing TIPS creation were studied during standard clinical applications. Patients were anesthetized and then positioned in an open MR unit containing a flat-panel radiographic fluoroscopic unit. With use of a combination of fluoroscopy and MR imaging, the PV was accessed and the TIPS procedure was performed. A noncovered nitinol stent or a covered stent-graft was placed in the TIPS tract. Number of punctures required, total procedure time, fluoroscopy time, procedural success rate, complications, and ultrasonographic and clinical follow-up were recorded. RESULTS: Clinical success was obtained in 13 of 14 patients. In one patient, extrahepatic puncture of the PV occurred, resulting in hemorrhage and requiring placement of a covered stent to control the bleeding. The mean number of punctures required to access the PV was 2.6 +/- 1.7, and the total procedure time was 2.5 hours +/- 0.6. Mean fluoroscopy time was 22.3 minutes +/- 5.5. Results of clinical and ultrasonographic follow-up compare favorably to previously published reports. CONCLUSION: TIPS creation with a combination hybrid radiography/MR unit is feasible and may reduce the number of needle passes required and radiation exposure, with similar overall outcomes compared with studies reported in the literature.

Stent-graft treatment of extracranial carotid and vertebral arterial lesions.

Five patients with pseudoaneurysms of the carotid artery (n = 4) and an arteriovenous fistula of the vertebral artery (n = 1) were treated with stent-grafts. Commercially made devices were used in all but one of the patients. In four of the five patients, the pathology was successfully excluded. One patient had a small type-I endoleak. There were no immediate procedure-related complications or neurologic sequalae. All experienced immediate resolution of symptoms. One patient was lost to follow-up after discharge and another died 2 weeks after intervention. The remaining patients remained asymptomatic with patent stent-grafts after follow-up periods of 14, 16, and 46 months, respectively.

The "Y" stent: a technique using nitinol stents to treat bifurcations.

PURPOSE: To investigate a new method of stent deployment using commercially available self-expanding stents to treat bifurcation lesions, providing complete lesion coverage without obstructing branches. METHODS: After preliminary in vitro and clinical testing with biliary obstructions, 11 vascular obstructive lesions in 10 patients (7 men; mean age 63 years, range 32-81) were treated by percutaneous Y-shaped stenting. Five patients had iliac arterial stenoses involving the iliac bifurcation; the other 5 patients had 6 central venous obstructions involving branch points. Bifurcated stents were constructed in situ by deploying a nitinol stent extending into one branch and selective balloon fracturing of struts to create a fenestration. A second stent was deployed through the hole, followed by symmetrical fracturing of struts in the second stent to form a Y-shaped configuration. RESULTS: All deployments were technically successful and resulted in complete coverage of the bifurcation lesions. Protrusion of fractured stent material into flow lumens was minor as determined by angiography, intravascular ultrasound, and passage of balloons, but it required the stents to be oversized. The lengths and luminal diameters were tailored for each arm of the Y-shaped stents. CONCLUSIONS: In situ creation of a Y-shaped stent using 2 self-expanding nitinol stents is a feasible option with potential advantages in the treatment of obstructive lesions involving a bifurcation.

Novel intravascular ultrasound-guided method to create transintimal arterial communications: initial experience in peripheral occlusive disease and aortic dissection.

PURPOSE: To report our experience using a commercially available catheter-based system equipped with an intravascular ultrasound (IVUS) transducer to achieve controlled true lumen re-entry in patients undergoing subintimal angioplasty for chronic total occlusions (CTO) or aortic dissections. METHODS: During an 8-month period, 10 patients (6 men; mean age 73.4 years) with lower extremity (LE) ischemia from CTOs (n=7) or true lumen collapse from aortic dissections (n=3) were treated. Subintimal access and controlled re-entry of the CTOs were performed with a commercially available 6.2-F dual-lumen catheter, which contained an integrated 64-element phased-array IVUS transducer and a deployable 24-G needle through which a guidewire was passed once the target lumen was reached. The occluded segments were balloon dilated; self-expanding nitinol stents were deployed. In the aortic dissections, fenestrations were performed using the same device, with the IVUS unit acting as the guide. The fenestrations were balloon dilated and stented to support the true lumen. RESULTS: Time to effective re-entry ranged from 6 to 10 minutes (mean 7) in the CTOs; antegrade flow was restored in all 7 CTOs, and the patients were free of ischemic symptoms at up to 8-month follow-up. In the aortic dissection cases, the fenestrations equalized pressures between the lumens and restored flow into the compromised vessels. There were no complications related to the use of this device in any of the 10 patients. CONCLUSIONS: Our preliminary results demonstrate the feasibility of using this catheter-based system for subintimal recanalization with controlled re-entry in CTOs and for aortic flap fenestrations in aortic dissections. This approach can improve the technical success rate, reduce the time of the procedure, and minimize potential complications.

In-stent restenosis limitation with stent-based controlled-release nitric oxide: initial results in rabbits.

PURPOSE: To evaluate effect of controlled stent-based release of an NO donor to limit in-stent restenosis in rabbits. MATERIALS AND METHODS: Bioerodable microspheres containing NO donor or biodegradable polymer (polylactide-co-glycolide-polyethylene glycol) were prepared and loaded in channeled stents. Daily concentrations of NO release from NO-containing microspheres were assayed in vitro. NO- and polymer-containing (control) microsphere-loaded stents were deployed in aortas of New Zealand white rabbits (n = 8). Aortas with stents were harvested at 7 (n = 5) and 28 days (n = 3) and evaluated for cyclic guanosine monophosphate (cGMP) levels (7 days), number of proliferating cell nuclear antigen-positive cells (7 days), and intima-to-media ratio (7 and 28 days), with statistical significance evaluated by using one-way analysis of variance. RESULTS: NO-containing microspheres released NO with an initial bolus in the 1st week, followed by sustained release for the remaining 3 weeks. Significant increase in cGMP levels and decrease in proliferating cell nuclear antigen-positive cells were found at 7 days for the NO-treated group relative to controls (P <.05). Intima-to-media ratio in the NO-treated group was reduced by 46% and 32% relative to controls at 7 and 28 days, respectively (mean, 0.14 +/- 0.01 [standard error] vs 0.26 +/- 0.02 at 7 days, P <.01; 1.34 +/- 0.05 vs 1.98 +/- 0.08 at 28 days, P <.01). CONCLUSION: Stent-based controlled release of NO donor significantly reduces in-stent restenosis and is associated with increase in vascular cGMP and suppression of proliferation.

Stent-based controlled release of intravascular angiostatin to limit plaque progression and in-stent restenosis.

PURPOSE: To evaluate the importance of angiogenesis in plaque progression after stent placement, this study examines stent-based controlled delivery of the antiangiogenic agent, angiostatin, in a rabbit model. MATERIALS AND METHODS: Controlled release biodegradable microspheres delivering angiostatin or polymer-only microspheres (polylactic-co-glycolic-acid-polyethylene glycol; PLGA/PEG) were loaded in channeled stents, anchored, and deployed in the aorta of adult New Zealand white rabbits (n = 6 animals per group, three each per time point). The stented aortas were harvested at 7 days and 28 days and evaluated for neovascularization, local inflammation, vascular smooth muscle cell proliferation, and in-stent plaque progression. RESULTS: At 7 days, neovascularization was significantly decreased in the angiostatin groups (1.6 +/- 1.6 neovessels per mm(2) plaque) versus the control group (15.4 +/- 2.6 neovessels per mm(2) plaque; P =.00081), as were local inflammation where angiostatin-treated groups demonstrated significantly lower macrophage recruitment per cross section (34.9 +/- 4.9 cells per cross section) relative to the control group (55.2 +/- 3.84 cells per cross section; P =.0037). And a significant decrease in the overall vascular smooth muscle cell proliferation (143.8 +/- 26.3 Ki-67 positive cells per mm(2)) relative to the control group (263.2 +/- 16.6 Ki-67 positive cells per mm(2); P =.00074). At both 7 and 28 days, in-stent plaque progression in the angiostatin groups was successfully limited relative to the control group by 54% (0.255 +/- 0.019% of cross section; P =.00016) and 19% (1.981 +/- 0.080; P =.0033) respectively and resulted in reduction of in-stent restenosis relative to the control group. CONCLUSION: Angiostatin-eluting stents may limit neovascularity after arterial implantation, offer insight into in-stent restenosis, and allow future refinement of bioactive stent designs and clinical strategies, particularly in light of evidence that intimal smooth muscle cells may in part be marrow-derived.