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.

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.

The United States StuDy for EvalUating EndovasculaR TreAtments of Lesions in the Superficial Femoral Artery and Proximal Popliteal By usIng the Protégé EverfLex NitInol STent SYstem II (DURABILITY II).

OBJECTIVE: Angioplasty and stenting are options for revascularization of symptomatic femoral popliteal disease. Although angioplasty alone is effective in short lesions, longer lesions are often treated with stents. Multiple overlapping stents are expensive and may be associated with stent fracture. This trial evaluated the safety and efficacy of a single self-expanding stent up to 20 cm in length in patients with atherosclerotic disease of the superficial femoral artery (SFA) and proximal popliteal artery. METHODS: Patients with lesions >4 cm and <18 cm were enrolled in this nonrandomized, prospective, multicenter trial that evaluated the Protégé EverFlex Self-Expanding Peripheral Stent System (Covidien, Plymouth, Minn). The study's primary end points were the 30-day major adverse event rate and duplex ultrasound-assessed patency at 1 year. These were compared with published performance goals. A preplanned analysis was conducted for the primary effectiveness end points at 1 year. Follow-up, including history, ankle-brachial index, patient-reported outcomes, duplex ultrasound assessment, and radiographs, is planned through 3 years. There was core laboratory review of angiograms, ultrasound scans, and plain radiographs. A subgroup of patients was studied with graded treadmill testing. RESULTS: The study enrolled 287 patients (66% male; mean age, 68 years) with stenotic, restenotic, or occluded lesions of the SFA at 44 investigational sites in the United States and Europe. Systemic comorbidities included hypertension (88%), hyperlipidemia (86%), diabetes (43%), and prior SFA intervention (41%). The mean lesion length measured by the core laboratory was 89 mm. The mean normal-to-normal lesion length measured by sites was 110 mm. A total of 303 stents were implanted, and 95% of patients received a single stent. No major adverse events occurred at 30 days. At 1 year, primary outcome of duplex ultrasound stent patency was 67.7% in evaluable patients, and among 1-year secondary outcomes, the mean ankle-brachial index increased by 0.25. Walking Improvement Questionnaire scores improved in pain by 33.7, distance by 37.1, speed by 18.6, and stair climbing by 24.7. The Kaplan-Meier estimate of primary patency was 77.2%, primary assisted patency was 86.9%, and secondary patency was 87.3%. Rutherford clinical category improved in 83.5% of patients. Stent fracture rate was 0.4%. Matched absolute claudication distance was 412 feet greater and was not statistically different in this subgroup of 29 individuals. CONCLUSIONS: The results of DURABILITY II (StuDy for EvalUating EndovasculaR TreAtments of Lesions in the Superficial Femoral Artery and Proximal Popliteal By usIng the Protégé EverfLex NitInol Stent SYstem II) suggest that a new single stent strategy is safe and effective for the treatment of long lesions of the SFA and proximal popliteal arteries at 1 year.

Comparison of Drug-Coated Balloons vs Bare-Metal Stents in Patients With Femoropopliteal Arterial Disease.

BACKGROUND: Endovascular treatment of femoropopliteal artery disease has shifted toward drug-coated balloons (DCB). However, limited data are available regarding the safety and efficacy of DCB vs bare-metal stents (BMS). OBJECTIVES: The purpose of this study was to compare DCB vs BMS outcomes in a propensity-adjusted, pooled analysis of 4 prospective, multicenter trials. METHODS: Patient-level data were pooled from 4 prospective, multicenter studies: the IN.PACT SFA I/II and IN.PACT SFA Japan randomized controlled DCB trials and the Complete SE and DURABILITY II single-arm BMS studies. Outcomes were compared using inverse probability of treatment weighting (IPTW). Clinical endpoints were 12-month primary patency, freedom from 36-month clinically driven target lesion revascularization, and cumulative 36-month major adverse events (MAE). RESULTS: The primary analysis included 771 patients (288 DCB, 483 BMS). IPTW-adjusted demographic, baseline lesion, and procedural characteristics were matched between groups. The adjusted mean lesion length was 8.1 ± 4.7 cm DCB and 7.9 ± 4.5 cm BMS. The IPTW-adjusted Kaplan-Meier estimates of 12-month primary patency (90.4% DCB, 80.9% BMS, P = 0.007), freedom from 36-month clinically driven target lesion revascularization (85.6% DCB, 73.7% BMS, P = 0.001), and cumulative incidence of 36-month MAE (25.3% DCB, 38.8% BMS, P < 0.001) favored DCB. There were no statistically significant differences observed in all-cause mortality, target limb major amputation, or thrombosis through 36 months. CONCLUSIONS: In a patient-level, IPTW-adjusted pooled analysis of prospective, multicenter pivotal studies, DCB demonstrated significantly higher patency, lower revascularization and MAE rates, and no statistically significant differences in mortality, amputation, or thrombosis vs BMS. This analysis supports DCB use vs BMS in moderately complex femoropopliteal lesions amenable to both treatments.

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.

Directional Atherectomy Followed by a Paclitaxel-Coated Balloon to Inhibit Restenosis and Maintain Vessel Patency: Twelve-Month Results of the DEFINITIVE AR Study.

BACKGROUND: Studies assessing drug-coated balloons (DCB) for the treatment of femoropopliteal artery disease are encouraging. However, challenging lesions, such as severely calcified, remain difficult to treat with DCB alone. Vessel preparation with directional atherectomy (DA) potentially improves outcomes of DCB. METHODS AND RESULTS: DEFINITIVE AR study (Directional Atherectomy Followed by a Paclitaxel-Coated Balloon to Inhibit Restenosis and Maintain Vessel Patency-A Pilot Study of Anti-Restenosis Treatment) was a multicenter randomized trial designed to estimate the effect of DA before DCB to facilitate the development of future end point-driven randomized studies. One hundred two patients with claudication or rest pain were randomly assigned 1:1 to DA+DCB (n=48) or DCB alone (n=54), and 19 additional patients with severely calcified lesions were treated with DA+DCB. Mean lesion length was 11.2±4.0 cm for DA+DCB and 9.7±4.1 cm for DCB (P=0.05). Predilation rate was 16.7% for DA+DCB versus 74.1% for DCB; postdilation rate was 6.3% for DA+DCB versus 33.3% for DCB. Technical success was superior for DA+DCB (89.6% versus 64.2%; P=0.004). Overall bail-out stenting rate was 3.7%, and rate of flow-limiting dissections was 19% for DCB and 2% for DA+DCB (P=0.01). One-year primary outcome of angiographic percent diameter stenosis was 33.6±17.7% for DA+DCB versus 36.4±17.6% for DCB (P=0.48), and clinically driven target lesion revascularization was 7.3% for DA+DCB and 8.0% for DCB (P=0.90). Duplex ultrasound patency was 84.6% for DA+DCB, 81.3% for DCB (P=0.78), and 68.8% for calcified lesions. Freedom from major adverse events at 1 year was 89.3% for DA+DCB and 90.0% for DCB (P=0.86). CONCLUSIONS: DA+DCB treatment was effective and safe, but the study was not powered to show significant differences between the 2 methods of revascularization in 1-year follow-up. An adequately powered randomized trial is warranted. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique Identifier: NCT01366482.

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.