Directional atherectomy before paclitaxel coated balloon angioplasty in complex femoropopliteal disease: The VIVA REALITY study.

BACKGROUND: Drug coated balloon (DCB) angioplasty significantly reduces reintervention rates in patients with symptomatic femoropopliteal peripheral artery disease (PAD). However, stand-alone DCB use in long, severely calcified lesions is frequently associated with vessel recoil and/or high-grade dissections necessitating provisional stent implantation. OBJECTIVES: Assess the safety and effectiveness of a vessel preparation strategy with directional atherectomy (DA) prior to DCB angioplasty in patients with symptomatic severely calcified femoropopliteal PAD. METHODS: REALITY (NCT02850107) prospectively enrolled subjects at 13 multinational centers with 8-36 cm femoropopliteal stenoses or occlusions with bilateral vessel wall calcification treated with DA prior to DCB angioplasty. The primary effectiveness endpoint was 12-month primary patency, and the primary safety endpoint was freedom from major adverse events through 30 days. Independent angiographic and duplex core laboratories assessed outcomes and a Clinical Events Committee adjudicated events. RESULTS: A total of 102 subjects were enrolled; one lesion was treated per subject. The mean lesion length was 17.9 ± 8.1 cm, 39.0% were chronic total occlusions (mean lesion length 22.6 ± 8.6 cm); 86.2% of lesions exhibited moderate to severe bilateral calcification. Provisional stents were implanted in 8.8% (9/102) of subjects. Twelve-month primary patency rate was 76.7% (66/86) and freedom from CD-TLR rate was 92.6% (87/94). No device or procedure related deaths and one index-limb major amputation were reported. CONCLUSIONS: Plaque excision with DA in patients with symptomatic severely calcified femoropopliteal arterial disease prior to DCB angioplasty is a safe and effective treatment strategy with a low provisional stent rate.

Paclitaxel exposure: Long-term safety and effectiveness of a drug-coated balloon for claudication in pooled randomized trials.

BACKGROUND: Paclitaxel drug-coated balloons (DCB) prevent recurrent claudication after angioplasty, yet data from randomized trials with incomplete follow-up have raised uncertainty regarding long-term mortality. OBJECTIVES: To evaluate the effect of paclitaxel exposure on the long-term safety and efficacy of angioplasty of femoropopliteal artery lesions in the combined IN.PACT randomized trials. METHODS: The IN.PACT randomized trials (SFA, N = 331 and Japan, N = 100) each compared the DCB with standard percutaneous transluminal angioplasty (PTA) for claudication, and consented patients for 5 and 3 years, respectively. To address long-term safety, sites were requested to obtain vital status follow-up. In the pooled, updated data set, we examined the association between randomized treatment and mortality by cumulative incidence and hazard ratio (HR), and freedom from clinically driven target lesion revascularization (CD-TLR). Multivariable Cox regression with adjustment for baseline characteristics was used to evaluate the dose effect. Causes of death were adjudicated by a blinded clinical events committee that included oncologists with paclitaxel expertise. RESULTS: The rate of long-term vital status ascertainment increased from 81% to 97% for DCB and from 85% to 97% for PTA in the IN.PACT SFA trial. The cumulative incidence of mortality was 14.7% DCB versus 12.0% PTA at 5 years, HR 1.39, log-rank p = .286. Paclitaxel dose (mg) was not an independent predictor of mortality (HR 1.02, p = .381), but was an independent predictor of reduced risk of CD-TLR (HR 0.79; p < .001). Causes of death did not differ by treatment arm. CONCLUSIONS: In pooled randomized trial data with updated vital status ascertainment, paclitaxel was associated with improved efficacy but was not associated with increased mortality.

Design and rationale of a randomized noninferiority trial to evaluate the SurVeil drug-coated balloon in subjects with stenotic lesions of the femoropopliteal artery - the TRANSCEND study.

BACKGROUND: Drug-coated balloons (DCBs), developed to reduce restenosis after percutaneous intervention in peripheral arterial disease (PAD), have been shown to be safe and efficacious, particularly in treating PAD affecting the femoropopliteal segment. The SurVeil DCB uses an excipient intended to optimize both the uniformity and transfer of paclitaxel to the vessel wall, allowing for efficient drug loading and lower systemic exposure than currently available DCBs, Heretofore, clinical outcomes have not previously been compared to other DCBs. STUDY DESIGN AND OBJECTIVES: This prospective, multicenter, international, randomized, single-blind, trial will compare 1:1 the SurVeil DCB with the IN.PACT Admiral DCB for treatment of patients with Rutherford classification 2 to 4 due to femoral and/or popliteal arterial disease. The trial will randomize 446 subjects (with reference vessel diameter 4-7 mm and total lesion length ≤180 mm). Subjects will be followed for 60 months. The primary efficacy endpoint is 1 year primary patency, defined as composite freedom from clinically-driven target-lesion revascularization (TLR) and binary restenosis (core lab-adjudicated duplex ultrasound peak systolic velocity ratio ≥2.4, or ≥50% stenosis via angiography). The primary safety endpoint is composite freedom from device- and procedure-related death through 30 days and freedom from target limb major amputation and clinically-driven target vessel revascularization through 12 months. The primary analysis is a test of noninferiority of the SurVeil vs. IN.PACT Admiral on the primary efficacy and safety endpoints according to absolute deltas of 15.0% and 10.0%, respectively. CONCLUSION: The Randomized And Controlled Noninferiority Trial to Evaluate Safety and Clinical Efficacy of the SurVeil DCB in the Treatment of Subjects with Stenotic Lesions of the Femoropopliteal Artery Compared to the Medtronic IN.PACT Admiral (TRANSCEND) study will assess safety and efficacy of the SurVeil DCB relative to a commonly used DCB.

Full Drug-Eluting Stent Jacket: Two-Year Results of a Single-Center Experience With Zilver PTX Stenting for Long Lesions in the Femoropopliteal Arteries.

PURPOSE: To evaluate the 1- and 2-year patency and reintervention rates with the Zilver PTX drug-eluting stent (DES) in long complex femoropopliteal disease. METHODS: A retrospective review was conducted of 89 consecutive patients (mean age 68.7±9.8 years; 86 men) with femoropopliteal occlusive disease (Rutherford category 2-6) treated with the Zilver PTX between December 2012 and December 2013. Mean lesion length for the entire cohort was 24.2±11.3 cm (median 24.0, range 4-48). The patient population was dichotomized into a short lesion (≤20 cm) group (n=41; mean lesion length 13.3±5.6 cm) and the full DES jacket (>20 cm) group (n=48; mean lesion length 33.0±6.5 cm). Primary endpoints were duplex-derived restenosis (peak systolic velocity ratio >2.5), clinically driven reintervention, and major amputation. RESULTS: The incidence of restenosis was lower in the short lesion group at 1 year (19% vs 40% for the longer lesions, p=0.050) and 2 years (39% vs 54%, respectively; p=0.331). The short lesion group had significantly lower rates of reintervention at both 1 year (2% vs 21% in long lesions, p=0.009) and 2 years (12% vs 33%, p=0.019). CONCLUSION: Treatment of femoropopliteal lesions >20 cm with the Zilver PTX appears to be a clinically effective therapy for patients with symptomatic peripheral artery disease. However, there is an increase in restenosis and a need for reintervention that continues to progress up to 2 years.

Drug-Coated Balloon Treatment of Femoropopliteal Lesions Typically Excluded From Clinical Trials: 12-Month Findings From the IN.PACT Global Study.

PURPOSE: To report a post hoc analysis comparing outcomes between subjects who would have been included in the IN.PACT SFA randomized controlled trial vs those who would have been excluded. METHODS: The 1406 subjects enrolled in the IN.PACT Global Study ( ClinicalTrials.gov identifier NCT01609296) were retrospectively assigned to a standard-use group (n=281) based on the inclusion and exclusion criteria from the randomized IN.PACT SFA trial; the remaining 1125 patients were assigned to the broader-use group. Freedom from clinically-driven target lesion revascularization (CD-TLR) was evaluated at 12 months. The composite primary safety endpoint was freedom from 30-day device- and procedure-related death plus freedom from 12-month target limb major amputation and clinically-driven target vessel revascularization (CD-TVR). Functional outcomes were evaluated with dedicated questionnaires. RESULTS: Compared with the standard-use cohort, the broader-use lesions were longer, more calcified, and had more popliteal involvement, bilateral disease, and in-stent restenosis (p<0.001 for all). Freedom from 12-month CD-TLR by Kaplan-Meier analysis was 96.6% for the standard-use group and 91.6% for the broader-use group (p=0.005). The safety endpoint was 96.2% in the standard-use group and 91.0% in the broader-use group (p=0.003). The 12-month CD-TLR (3.4% standard-use vs 8.5% broader-use, p=0.004) and CD-TVR (4.2% standard-use vs 9.1% broader-use, p=0.008) were increased in the broader-use group. Twelve-month all-cause mortality was not increased (3.8% standard-use vs 3.4% broader-use, p=0.852). CONCLUSION: Post hoc analysis of the IN.PACT Global Study of real-world patients demonstrated consistent outcomes with significant clinical improvement to 12 months in subjects with complex lesions typically excluded from a randomized controlled trial.

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.

Five-Year Safety and Effectiveness of Paclitaxel Drug-Coated Balloons Alone or With Provisional Bare Metal Stenting for Real-World Femoropopliteal Lesions: IN.PACT Global Study Subgroup Analysis.

BACKGROUND: The treatment of complex infra-inguinal disease with drug-coated balloons (DCBs) is associated with a significant number of patients undergoing provisional stenting to treat a suboptimal result. To determine the potential long-term impact of DCB treatment with provisional bare metal stenting in complex lesions in real-world patients, a post hoc analysis was performed on data from the IN.PACT Global Study (The IN.PACT Global Clinical Study for the Treatment of Comprehensive Superficial Femoral and/or Popliteal Artery Lesions Using the IN.PACT Admiral Drug-Eluting Balloon). Five-year outcomes were compared between participants who were stented after DCB treatment versus those treated with DCB alone. METHODS: The IN.PACT Global Study enrolled 1535 participants with intermittent claudication and/or ischemic rest pain caused by femoropopliteal lesions; 1397 patients were included in this subgroup analysis (353 stented and 1044 nonstented). Effectiveness was assessed as freedom from clinically driven target lesion revascularization through 60 months. The primary safety composite end point was defined as freedom from device- and procedure-related death through 30 days, and freedom from major target limb amputation and clinically driven target vessel revascularization through 60 months. RESULTS: Lesions in the stented group were longer (15.37 versus 10.98 cm; P<0.001) and had more total occlusions (54.7% versus 28.6%; P<0.001) compared with the nonstented group. The 5-year Kaplan-Meier estimated freedom from clinically driven target lesion revascularization was similar between groups (66.8% stented versus 70.0% nonstented group, log-rank P=0.22). The safety composite end point was achieved in 64.5% stented versus 68.2% nonstented participants (log-rank P=0.19) as estimated by the Kaplan-Meier method. No significant difference was observed in the cumulative incidence of major adverse events (49.1% stented versus 45.0% nonstented; log-rank P=0.17), including all-cause death (19.6% stented versus 19.3% nonstented, log-rank P=0.99). CONCLUSIONS: In this real-world study, revascularization of complex femoropopliteal artery lesions with DCB angioplasty alone or DCB followed by provisional bare metal stenting in certain lesions achieved comparable long-term safety and clinical effectiveness. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01609296.

Three-year results of the VIBRANT trial of VIABAHN endoprosthesis versus bare nitinol stent implantation for complex superficial femoral artery occlusive disease.

OBJECTIVE: The predominant mode of bare nitinol stent failure is diffuse in-stent restenosis, and failure rates correlate to the length and complexity of the treated lesion. Addition of an expanded polytetrafluoroethylene lining to a nitinol stent frame, as found in the VIABAHN endoprosthesis, mitigates the ingrowth of intimal hyperplasia. We compared the long-term outcomes of complex superficial femoral artery disease intervention using the VIABAHN endoprosthesis to those obtained with bare nitinol stent implantation. METHODS: One hundred forty-eight patients with symptomatic complex superficial femoral artery disease (TransAtlantic Inter-Society Consensus I class C and D lesions, accompanied by intermittent claudication or ischemic rest pain) were randomized to endovascular intervention using either bare nitinol stent implantation (76 patients) or nonheparin-bonded VIABAHN endoprosthesis deployment (72 patients). Patency, limb hemodynamics, and quality of life were evaluated at 1, 6, 12, 24, and 36 months following intervention. RESULTS: The average treated lesion measured 18 ± 8 cm in length, and 58.8% of lesions displayed segmental or complete occlusion. At 3 years, primary patency rates (defined by peak systolic velocity ratio ≤ 2.0 and no target lesion revascularization) did not significantly differ between patients treated with the VIABAHN stent graft and those who received a bare nitinol stent (24.2% vs 25.9%; P = .392). Stent fractures were significantly more common in bare nitinol stents (50.0%) than in the VIABAHN endoprostheses (2.6%). Primary-assisted patency rates were higher in those receiving bare nitinol stents than the VIABAHN stent graft (88.8% vs 69.8%; P = .04), although secondary patency rates did not differ between bare nitinol stent and stent graft recipients (89.3% vs 79.5%; P = .304). There were no instances of procedure-related mortality or amputation. The hemodynamic improvement and quality measures improved equally in both groups. CONCLUSIONS: The long-term outcomes of complex superficial femoral artery disease intervention using the VIABAHN endograft and bare nitinol stents are similar. Although primary patency rates are low in both study arms, excellent primary-assisted and secondary patency rates were achieved, with sustained augmentation of limb perfusion and quality-of-life measures. Patency rates diminish most rapidly in the first year after device implantation.

Heparin-bonded, expanded polytetrafluoroethylene-lined stent graft in the treatment of femoropopliteal artery disease: 1-year results of the VIPER (Viabahn Endoprosthesis with Heparin Bioactive Surface in the Treatment of Superficial Femoral Artery Obstructive Disease) trial.

PURPOSE: To evaluate the performance of a heparin-bonded, expanded polytetrafluoroethylene (ePTFE)-lined nitinol endoprosthesis in the treatment of long-segment occlusive disease of the femoropopliteal artery (FPA) and to identify factors associated with loss of patency. MATERIALS AND METHODS: In a single-arm, prospective, 11-center study (VIPER [Gore Viabahn Endoprosthesis with Heparin Bioactive Surface in the Treatment of Superficial Femoral Artery Obstructive Disease] trial), 119 limbs (113 patients; 69 men; mean age, 67 y), including 88 with Rutherford category 3-5 disease and 72 with Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II) C or D lesions of the FPA, underwent stent graft implantation. The mean lesion length was 19 cm; 56% of lesions were occlusions. Follow-up evaluations included color duplex ultrasonography in all patients, with patency defined as a peak systolic velocity ratio< 2.5. RESULTS: At 12 months, Rutherford category and ankle-brachial index (ABI) were significantly improved (mean category improvement, 2.4; ABI increased from 0.6±0.2 to 0.9±0.19; P<.0001). Primary and secondary patency rates were 73% and 92%. The primary patency for devices oversized<20% at the proximal landing zone was 88%, whereas the primary patency for devices oversized by>20% was 70% (P = .047). Primary patency was not significantly affected by device diameter (5 vs 6 vs 7 mm) or lesion length (≤20 cm vs>20 cm). The 30-day major adverse event rate was 0.8%. CONCLUSIONS: The heparin-bonded, ePTFE/nitinol stent graft provided clinical improvement and a primary patency rate of 73% at 1 year in the treatment of long-segment FPA disease. Careful sizing of the device relative to vessel landing zones is essential for achieving optimal outcomes.

Major adverse limb events and wound healing following infrapopliteal artery stent implantation in patients with critical limb ischemia: the XCELL trial.

BACKGROUND: Percutaneous transluminal angioplasty (PTA) with stent deployment of infrapopliteal arteries is an accepted but unproven therapy for patients with critical limb ischemia (CLI). We evaluated the safety and effectiveness of the Xpert™ self-expanding nitinol stent (Abbott Vascular, Redwood City, CA) in Rutherford Class 4-6 subjects with infrapopliteal lesions of 4-15 cm in length. METHODS AND RESULTS: 120 patients (140 limbs, 212 implanted devices) underwent primary infrapopliteal nitinol stent deployment as part of this multicenter registry. The primary endpoint was 12-month amputation-free survival (AFS); secondary endpoints included limb salvage, target lesion revascularization (TLR), 6- month angiographic patency, and 6- and 12-month outcomes of wound healing and pain relief. Despite a 6-month binary stent restenosis rate of 68.5%, the 12-month AFS rate was 78.3%. Stratified according to baseline Rutherford classes 4, 5 and 6, the 12-month AFS rates were 100%, 77.3%, and 55.2%, respectively, and freedom from major amputation rates were 100%, 90.9%, and 70.1%, respectively. The 12-month freedom from major amputation rate and clinically driven TLR were 89.6% and 70.1%, respectively. The 6- and 12-month complete wound-healing rates were 49.0% and 54.4%, respectively. Rutherford class 4 patients had significant pain relief through 12-months (P<0.05). CONCLUSIONS: Primary infrapopliteal nitinol stenting to treat CLI is safe and effective in improving 6-and 12-month clinical outcomes.

Nitinol stent implantation vs. balloon angioplasty for lesions in the superficial femoral and proximal popliteal arteries of patients with claudication: three-year follow-up from the RESILIENT randomized trial.

PURPOSE: To evaluate longer outcomes of primary nitinol stenting for the treatment of femoropopliteal lesions up to 15 cm long after these stents were found to have superior short-term patency vs. balloon angioplasty. METHODS: Two hundred and six patients (143 men; mean age 67 years) with intermittent claudication due to superficial femoral and proximal popliteal artery lesions were randomized (2:1) to treatment with nitinol stents or balloon angioplasty at 24 US and European centers and followed for 3 years. In that time, 15 patients died, 20 withdrew consent, and 10 were lost to follow-up, leaving 161 (78.2%) patients for 36-month assessment. RESULTS: The 12-month freedom from target lesion revascularization (TLR) was 87.3% for the stent group vs. 45.2% for the angioplasty group (p<0.0001). At 3 years, there was no difference in survival (90.0% vs. 91.7%, p=0.71) or major adverse events (75.2% vs. 75.2%, p=0.98) between the stent and angioplasty groups. Duplex ultrasound was not mandated after the first year, so stent patency could not be ascertained beyond 1 year, but freedom from TLR at 3 years was significantly better in the stent group (75.5% vs. 41.8%, p<0.0001), as was clinical success (63.2% vs. 17.9%, p<0.0001). At 18 months, a 4.1% (12/291) stent fracture rate was documented. CONCLUSION: In this multicenter trial, primary implantation of a nitinol stent for moderate-length lesions in the femoropopliteal segment of patients with claudication was associated with better long-term results vs. balloon angioplasty alone.

Drug-coated balloons versus drug-eluting stents in the femoropopliteal artery: comparing apples to oranges?

Superficial femoral and popliteal artery disease are commonly involved in the development of symptomatic PAD. As time has gone on drug coated stents and drug coated balloons have supplanted the plain balloon angioplasty corner stone of therapy with superiority proven in randomized trials. Device approval trials are typically characterized by simple lesions that are less common than the longer complex disease. Registry data has demonstrated benefit of both technologies though drug coated balloons typically require a significant amount of adjunctive stenting in more complex disease. Recently published randomized data is starting to help proceduralists define when each therapy may be more optimal.

Mortality Not Correlated With Paclitaxel Exposure: An Independent Patient-Level Meta-Analysis of a Drug-Coated Balloon.

BACKGROUND: Five years of prospective clinical trials confirm that the paclitaxel drug-coated balloon (DCB) (IN.PACT Admiral, Medtronic, Dublin, Ireland) is safe and effective to treat femoropopliteal artery disease. A recent meta-analysis of heterogeneous trials of paclitaxel-based balloons and stents reported that they are associated with increased mortality and that higher doses are linked to higher mortality from 2 to 5 years. OBJECTIVES: The purpose of this study was to determine if there is a correlation between paclitaxel exposure and mortality by conducting an independent patient-level meta-analysis of 1,980 patients with up to 5-year follow-up. METHODS: Data from 2 single-arm and 2 randomized independently adjudicated prospective studies of a paclitaxel DCB (n = 1,837) and uncoated percutaneous transluminal angioplasty (PTA) (n = 143) were included. Analyses of baseline, procedure, and follow-up data of individual patients were performed to explore correlations of paclitaxel dose with long-term mortality. Survival time by paclitaxel dose tercile was analyzed with adjustment of inverse probability weighting to correct baseline imbalances and study as random effect. A standard cohort was defined to compare DCB- and PTA-treated patients with similar characteristics by applying criteria from pivotal studies (n = 712 DCB, n = 143 PTA). RESULTS: A survival analysis stratified nominal paclitaxel dose by low, mid, and upper terciles; mean doses were 5,019.0, 10,007.5, and 19,978.2 µg, respectively. Rates of freedom from all-cause mortality between the 3 groups through 5 years were 85.8%, 84.2%, and 88.2%, respectively (p = 0.731). There was no significant difference in all-cause mortality between DCB and PTA through 5 years comparing all patients (unadjusted p = 0.092) or patients with similar characteristics (adjusted p = 0.188). CONCLUSIONS: This independent patient-level meta-analysis demonstrates that this paclitaxel DCB is safe. Within DCB patients, there was no correlation between level of paclitaxel exposure and mortality. (Randomized Trial of IN.PACT Admiral® Drug Coated Balloon vs Standard PTA for the Treatment of SFA and Proximal Popliteal Arterial Disease [INPACT SFA I], NCT01175850; IN.PACT Admiral Drug-Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Superficial Femoral Artery [SFA] and Proximal Popliteal Artery [PPA] [INPACT SFA II], NCT01566461; MDT-2113 Drug-Eluting Balloon vs. Standard PTA for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery and/or Proximal Popliteal Artery [MDT-2113 SFA], NCT01947478; The IN.PACT SFA Clinical Study for the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery and/or Proximal Popliteal Artery Using the IN.PACT Admiral™ Drug-Eluting Balloon in a Chinese Patient Population, NCT02118532; and IN.PACT Global Clinical Study, NCT01609296).

Helical Centerline Stent Improves Patency: Two-Year Results From the Randomized Mimics Trial.

BACKGROUND: Reintervention in the femoropopliteal artery is frequent and a major driver of cost-effectiveness. High wall shear generated by swirling blood flow is associated with reduced occurrence of atherosclerosis and restenosis. This trial investigated the clinical and hemodynamic outcomes of the BioMimics 3D self-expanding tubular nitinol stent with helical centerline geometry compared with a straight stent in the femoropopliteal artery. METHODS AND RESULTS: In a prospective, multicenter, randomized controlled trial, 76 patients with symptomatic peripheral arterial disease were randomized 2:1 to receive a helical or a straight stent. An independent core laboratory adjudicated angiographic and ultrasound parameters. The primary safety end point was freedom from a composite of all death, target limb amputation, and target lesion revascularization at 30 days. The primary effectiveness end point was freedom from clinically driven target lesion revascularization at 6 months. Patency was a secondary end point. Subjects were followed up for 2 years from intervention. The primary safety (1-sided P<0.01) and efficacy (1-sided P<0.001) end points for the helical stent were met. The proportion of patients treated with the helical stent who maintained patency at 12 and 24 months was 80% and 72%, respectively, compared with 71% and 55% for the control group. The difference was significant through 24 months (P=0.05). Freedom from clinically driven target lesion revascularization for the helical compared with straight stent was 91% versus 92% at 12 months and 91% versus 76% at 24 months. CONCLUSIONS: Both groups had similar safety outcomes and clinically driven target lesion revascularization to 2 years. However, after placement of a BioMimics 3D helical stent, there was improved patency to 2 years. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02163863.

Nitinol stent implantation versus balloon angioplasty for lesions in the superficial femoral artery and proximal popliteal artery: twelve-month results from the RESILIENT randomized trial.

BACKGROUND: Controversy still exists regarding the best endovascular treatment strategy for patients with symptomatic disease of the superficial femoral artery. There are conflicting data regarding the benefits of superficial femoral artery stenting and the role of primary stenting compared with balloon angioplasty with provisional stent implantation. METHODS AND RESULTS: A total of 206 patients from 24 centers in the United States and Europe with obstructive lesions of the superficial femoral artery and proximal popliteal artery and intermittent claudication were randomized to implantation of nitinol stents or percutaneous transluminal angioplasty. The mean total lesion length was 71 mm for the stent group and 64 mm for the angioplasty group. Acute lesion success (<30%residual stenosis) was superior for the stent group compared with the angioplasty group (95.8% versus 83.9%; P<0.01). Twenty-nine (40.3%) patients in the angioplasty group underwent bailout stenting because of a suboptimal angiographic result or flow-limiting dissection. Bailout stenting was treated as a target lesion revascularization and loss of primary patency in the final analysis. At 12 months, freedom from target lesion revascularization was 87.3% for the stent group compared with 45.1% for the angioplasty group (P<0.0001). Duplex ultrasound-derived primary patency at 12 months was better for the stent group (81.3% versus 36.7%; P<0.0001). Through 12 months, fractures occurred in 3.1% of stents implanted. No stent fractures resulted in loss of patency or target lesion revascularization. CONCLUSIONS: In this multicenter trial, primary implantation of a self-expanding nitinol stent for moderate-length lesions in the superficial femoral artery and proximal popliteal artery was associated with better acute angiographic results and improved patency compared with balloon angioplasty alone. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00673985.

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.

Performance goals and endpoint assessments for clinical trials of femoropopliteal bare nitinol stents in patients with symptomatic peripheral arterial disease.

OBJECTIVE: This analysis proposes safety and performance goals for prospective single-arm trials of bare nitinol stents to treat patients with debilitating claudication associated with femoropopliteal (FP) atherosclerotic lesions. BACKGROUND: To date there have been no analyses of clinical trials data to set efficacy and safety benchmarks for new bare nitinol stents in the treatment of claudication from FP disease. Industry has been reluctant to sponsor studies of nitinol stents due to logistical barriers. METHODS: VIVA Physician's, Inc. (VPI) analyzed subject-level data from the PTA control arm of three randomized FDA device trials conducted by industry. Subjects with Rutherford category 2-4 claudication and FP lesion lengths 4-15 cm with 12 month duplex ultrasound (DUS) assessment were identified. These data were combined with the results of a survey of the medical literature (1990-2006) for similar subjects. RESULTS: Analysis of the industry derived control arm PTA data identified 116 patients (mean lesion length 8.7 cm) with a 12 month DUS defined FP patency of 28%. A similar cohort of 191 patients was identified from the medical literature in which the 12-month vessel patency equaled 37%; from these combined patient cohorts, expected vessel patency for PTA was estimated to equal 33%. CONCLUSION: Based on the PTA performance efficacy rate of 33% derived from industry clinical trial data and the medical literature, and the requirement that the bare nitinol stent 12-month efficacy performance goal be set to equal twice this rate, the patency efficacy goal equals 66%. Additional information is provided on safety and other reporting standards and stent integrity evaluation for bare metal stents.

Functional and clinical outcomes of nitinol stenting with and without abciximab for complex superficial femoral artery disease: a randomized trial.

OBJECTIVE: To evaluate the effect of glycoprotein IIb/IIIa inhibition during nitinol stenting, of superficial femoral occlusive disease. BACKGROUND: Stent implantation in the superficial femoral artery has been associated with suboptimal results while Glycoprotein IIb/IIIa inhibitors have shown improved procedural results during coronary intervention. We evaluated abciximab infusion during (Smart Stent) implantation in superficial femoral obstructions. METHODS: We conducted a randomized placebo controlled trial. The two primary end points include: (1) 9-month restenosis defined as a decrease in ankle brachial index and in-stent duplex ultrasound restenosis: (2) adverse events defined as death (30 days) or repeat revascularization within 9 months. RESULTS: Twenty-seven patients were randomized to abciximab and 24 patients to control (placebo). The primary end point of cumulative restenosis occurred in 15.4% of patients administered abciximab and in 12% administered placebo (P = 0.873). The primary restenosis endpoint in diabetics and total occlusions were similar at 14.3% and 15.4% respectively. The composite end point of 30-day mortality and 9-month revascularization occurred in 5.8% abciximab and 0% (P = 0.274) placebo with no 30-day deaths. Graded treadmill time and Rutherford class were all significantly improved in both groups, but the abciximab group did not appear to demonstrate any identifiable effect. CONCLUSION: (Smart Stent) nitinol stenting of the superficial femoral artery was associated with favorable functional outcomes at 9 months. Adjunctive abciximab did not appear to demonstrate any identifiable effect.