Efficacy of a Drug-Eluting Stent Versus Bare Metal Stents for Symptomatic Femoropopliteal Peripheral Artery Disease: Primary Results of the EMINENT Randomized Trial.

BACKGROUND: A clear patency benefit of a drug-eluting stent (DES) over bare metal stents (BMSs) for treating peripheral artery disease of the femoropopliteal segment has not been definitively demonstrated. The EMINENT study (Trial Comparing Eluvia Versus Bare Metal Stent in Treatment of Superficial Femoral and/or Proximal Popliteal Artery) was designed to evaluate the patency of the Eluvia DES (Boston Scientific, Marlborough, MA), a polymer-coated paclitaxel-eluting stent, compared with BMSs for the treatment of femoropopliteal artery lesions. METHODS: EMINENT is a prospective, randomized, controlled, multicenter European study with blinded participants and outcome assessment. Patients with symptomatic peripheral artery disease (Rutherford category 2, 3, or 4) of the native superficial femoral artery or proximal popliteal artery with stenosis ≥70%, vessel diameter of 4 to 6 mm, and total lesion length of 30 to 210 mm were randomly assigned 2:1 to treatment with DES or BMS. The primary effectiveness outcome was primary patency at 12 months, defined as independent core laboratory-assessed duplex ultrasound peak systolic velocity ratio ≤2.4 in the absence of clinically driven target lesion revascularization or surgical bypass of the target lesion. Primary sustained clinical improvement was a secondary outcome defined as a decrease in Rutherford classification of ≥1 categories compared with baseline without a repeat target lesion revascularization. Health-related quality of life and walking function were assessed. RESULTS: A total of 775 patients were randomly assigned to treatment with DES (n=508) or commercially available BMSs (n=267). Baseline clinical, demographic, and lesion characteristics were similar between the study groups. Mean lesion length was 75.6±50.3 and 72.2±47.0 mm in the DES and BMS groups, respectively. The 12-month incidence of primary patency for DES treatment (83.2% [337 of 405]) was significantly greater than for BMS (74.3% [165 of 222]; P<0.01). Incidence of primary sustained clinical improvement was greater among patients treated with the DES than among those who received a BMS (83.0% versus 76.6%; P=0.045). The health-related quality of life dimensions of mobility and pain/discomfort improved for the majority of patients in both groups (for 66.4% and 53.6% of DES-treated and for 64.2% and 58.1% of BMS-treated patients, respectively) but did not differ significantly. At 12 months, no statistical difference was observed in all-cause mortality between patients treated with the DES or BMS (2.7% [13 of 474] versus 1.1% [3 of 263]; relative risk, 2.4 [95% CI, 0.69-8.36]; P=0.15). CONCLUSIONS: By demonstrating superior 1-year primary patency, the results of the EMINENT randomized study support the benefit of using a polymer-based paclitaxel-eluting stent as a first-line stent-based intervention for patients with symptomatic peripheral artery disease attributable to femoropopliteal lesions. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02921230.

COMPARE: prospective, randomized, non-inferiority trial of high- vs. low-dose paclitaxel drug-coated balloons for femoropopliteal interventions.

AIMS: Drug-coated balloons (DCBs) for femoropopliteal interventions have not been tested against each other. We aimed to directly compare efficacy and safety of a high-dose (In.Pact™) vs. low-dose (Ranger™) DCB with nominal paclitaxel densities of 3.5 vs. 2.0 µg/mm2. METHODS AND RESULTS: Within a prospective, multicentre, non-inferiority, clinical trial 414 patients with symptomatic femoropopliteal lesions (Rutherford classification 2-4) were randomly assigned in a 1:1 ratio to endovascular treatment with either high- or low-dose DCB after stratification for lesion length. Primary efficacy and safety endpoints comprised primary patency and freedom from major adverse events (i.e. device and procedure-related deaths through 1 month, major amputations, and clinically driven target lesion revascularization through 12 months). We set a non-inferiority margin of -10% at 12 months. Total occlusions were observed frequently (>40%) and provisional stenting was performed in every fourth intervention. Non-inferiority was determined for both primary efficacy and safety endpoints at 12 months. Primary patency was 81.5% in the high-dose and 83.0% in low-dose DCB group {difference: 1.5% [lower bound of the 90% two-sided confidence interval (CI) -5.2%]; Pnon-inferiority < 0.01}. Freedom from major adverse events was determined in 92.6% in high-dose and in 91.0% in low-dose DCB group [difference -1.6% (lower bound of the 90% two-sided CI -6.5%); Pnon-inferiority < 0.01]. Overall death rate was low (2.0%) and no major amputation occurred. CONCLUSION: Two DCBs with different coating characteristics exhibited comparable results with excellent effectiveness and safety through 12 months for femoropopliteal interventions including a wide range of lesion lengths. CLINICAL TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov (NCT02701543).

Randomized Trial Comparing a Stent-Avoiding With a Stent-Preferred Strategy in Complex Femoropopliteal Lesions.

BACKGROUND: Limited comparative data exist on different interventional strategies for endovascular revascularization of complex femoropopliteal interventions. OBJECTIVES: In this study, the authors aimed to compare a stent-avoiding (SA) vs a stent-preferred (SP) strategy, promoting optimal lesion preparation and the use of drug-eluting technologies in both arms. METHODS: Within a prospective, multicenter, pilot study, 120 patients with symptomatic complex femoropopliteal lesions (Rutherford classification 2-4, mean lesion length 187.7 ± 78.3 mm, 79.2% total occlusions) were randomly assigned in a 1:1 fashion to endovascular treatment with either paclitaxel-coated balloons or polymer-coated, paclitaxel-eluting stents. Lesion preparation including the use of devices for plaque modification and/or removal was at the operators' discretion in both treatment arms. RESULTS: In the SA group, lesion preparation was more frequently performed (71.7% SA [43/60] vs 51.7% [31/60] SP; P = 0.038) with a high provisional stenting rate (48.3% [29/60]). At the 12-month follow-up, primary patency was 78.2% (43/55) in the SA group and 78.6% (44/56) in the SP group (P = 1.0; relative risk: 0.995; 95% CI: 0.818-1.210). Freedom from major adverse events was determined in 93.1% (54/58) in the SA group and in 94.9% (56/59) in the SP group (P = 0.717; relative risk: 0.981; 95% CI: 0.895-1.075), with all adverse events attributable to clinically driven target lesion revascularization. CONCLUSIONS: Both endovascular strategies promoting lesion preparation before the use of drug-eluting devices suggest promising efficacy and safety results in complex femoropopliteal procedures with a high proportion of total occlusions through 12 months. Ongoing follow-up will show whether different results emerge over time. (Best Endovascular Strategy for Complex Lesions of the Superficial Femoral Artery [BEST-SFA]; NCT03776799).

Clinical investigation of the GORE drug-coated PTA balloon catheter for CE mark approval.

OBJECTIVES: Paclitaxel-coated balloon angioplasty has been established as the first-line therapy for femoropopliteal artery disease. The primary objectives of the study were to evaluate the performance and the safety of the GORE-DCB Catheter in the treatment of atherosclerotic femoropopliteal lesions in patients with peripheral artery disease for CE-Mark approval. METHODS: Prospective, single-arm, multicenter study with 24 months follow-up. The GORE-DCB Catheter consists of a drug-coated nylon (inner layer)/ePTFE (outer layer) composite balloon. The ePTFE layer is coated with paclitaxel (concentration: 3.5 µg/mm2) and the excipient stearic acid/tromethamine (tris). The primary endpoints were 6-month late lumen loss (LLL) and 30-day of freedom from Major Adverse Events (MAE). RESULTS: Fifty-two subjects were enrolled, 69% men, median age 69 (49-83) years. Acute device success was 100%, the 30-day MAE rate was zero. Study primary endpoint of LLL (-0.17 mm) showed significant superiority compared to the performance goal of uncoated PTA balloon catheters from literature. At 1 and 2 years, primary patency rates were 81.8% and 68.7%, respectively, and freedom from clinically driven target lesion revascularization rates was 87.9% and 83.4%, respectively. CONCLUSION: The study demonstrates that the treatment of lesions in femoropopliteal arteries with the GORE-DCB Catheter is safe and effective.

Low-Dose vs High-Dose Paclitaxel-Coated Balloons for Femoropopliteal Lesions: 2-Year Results From the COMPARE Trial.

BACKGROUND: So far only 1-year data have been reported for direct comparisons of paclitaxel-coated balloons (PCBs) using different coating technologies. OBJECTIVES: The aim of this study was to report the 24-month results on the efficacy and safety of low-dose vs high-dose PCBs with nominal paclitaxel densities of 2.0 and 3.5 µg/mm2 and different coating technologies for femoropopliteal interventions from the COMPARE (Compare I Pilot Study for the Treatment of Subjects With Symptomatic Femoropopliteal Artery Disease) trial. Procedural characteristics of clinically driven (CD) target lesion revascularization (TLR) were analyzed. METHODS: Within a prospective, multicenter, clinical trial, 414 patients with symptomatic femoropopliteal lesions (Rutherford categories 2-4, maximum lesion length 30 cm) were randomly assigned in a 1:1 ratio to endovascular treatment with either a low-dose (Ranger) or a high-dose (IN.PACT) PCB after stratification for lesion length. Two-year follow-up included assessment of primary patency (defined as absence of CD TLR or binary restenosis with a peak systolic velocity ratio >2.4 by duplex ultrasound), safety, and functional and clinical outcomes. RESULTS: At 2 years, the Kaplan-Meier estimates of primary patency were 70.6% and 71.4% for the low-dose and high-dose PCBs (log-rank P = 0.96), respectively. One major amputation occurred in the high-dose group, and rates of all-cause mortality (3.6% vs 2.2%; P = 0.55) and CD TLR (17.3% vs 13.0%; P = 0.31) were similar between the groups. Among a total of 57 CD TLRs, 44.6% were performed for reocclusion and 28.1% for in-stent restenosis. Functional and clinical benefits over baseline were sustained in both groups. CONCLUSIONS: The 2-year results of the COMPARE trial demonstrate a sustained treatment benefit of both low-dose and high-dose PCBs for femoropopliteal interventions including a wide range of lesion lengths. (Compare I Pilot Study for the Treatment of Subjects With Symptomatic Femoropopliteal Artery Disease; NCT02701543).

Drug-Coated Balloon Angioplasty of Infrapopliteal Lesions in Patients with Critical Limb Ischaemia: 1-Year Results of the APOLLO Trial.

PURPOSE: This study intended to assess effectiveness and safety of the drug-coated balloon (DCB) angioplasty of infrapopliteal atherosclerotic lesions in patients with critical limb ischaemia (CLI) in a real-world setting. METHODS: Consecutive patients with critical limb ischaemia who underwent infrapopliteal drug-coated balloon angioplasty with the ELUTAX SV DCB were enrolled into the prospective, multicentre, single-arm observational registry. Primary outcome was clinical improvement at 6 and 12 months. Secondary outcomes were change in quality of life, primary patency, freedom from repeat revascularisation, and amputation-free survival at 6 and 12 months. RESULTS: A total of 164 patients (74.7 ± 9.2 years) with CLI were included at nine German sites between November 2015 and September 2017. The majority (79.9%) of patients had diabetes mellitus, 57.3% had renal insufficiency, and 35.3% had coronary artery disease. Mean lesion length was 71.2 ± 76.5 mm. The Rutherford category improved by 3.0 ± 2.0 (p < 0.0001) within 12 months, resulting in a clinical improvement by at least one Rutherford category in 80.2% of the patients. Walking impairment questionnaire score, European Quality of Life index, and patient-reported pain improved significantly from baseline to 6 and 12 months. Primary patency was 68.5%, freedom from target lesion revascularisation 90.6%, and amputation-free survival 83.5% at 12 months. CONCLUSION: Infrapopliteal drug-coated balloon angioplasty with the ELUTAX SV DCB in patients with critical limb ischaemia was efficacious and safe over the medium term. The study is registered with Clinical.Trials.gov (Identifier: NCT02539940).

Lutonix® 014 DCB global Below the Knee Registry Study: interim 6-month outcomes.

BACKGROUND: The most common clinical presentation of peripheral artery disease (PAD) comprises intermittent claudication (IC), but about one third of patients will progress to critical limb ischemia (CLI), characterized by rest pain and/or tissue loss, which is the most severe limb manifestation of PAD. Paclitaxel-coated balloons are well established for the endovascular treatment of femoropopliteal lesions in patients with IC and CLI. This ongoing multicenter registry study is exploring the role of the Lutonix® 014 drug-coated balloon (DCB) in the treatment of below-the-knee (BTK) arteries and CLI. METHODS: Three hundred fourteen (314) patients were enrolled from 26 sites and 12 countries. The real-world patients represent those undergoing intervention for BTK arteries with the Lutonix® 014 DCB. The study had both, primary safety and primary efficacy endpoints. The primary safety endpoint was freedom at 30 days from BTK major adverse limb event (MALE) + perioperative death (POD). Primary efficacy was freedom from clinically driven target lesion reintervention (fTLR) at 6 months. Additional secondary endpoints related to safety were reported. RESULTS: The interim 6 months' results showed freedom from MALE and POD at 30 days of 98.6% and at 6 months (180 days) of 96.0%. Primary efficacy of fTLR at 6 months (180 days) was 87.9%. Safety related secondary endpoints at 6 months (180 days) showed freedom from all of the following: all cause death of 91.2%, above ankle amputation 97.1%, reintervention for thrombosis 95.2%, reintervention for distal embolization 100.0%, and target vessel revascularization of 88.0%. There were no unexpected device or drug related events reported. CONCLUSIONS: The interim 6-month outcomes demonstrate the safety and efficacy of the Lutonix® 014 DCB for the treatment of BTK arteries.

The 24-Month Results of the Lutonix Global SFA Registry: Worldwide Experience With Lutonix Drug-Coated Balloon.

OBJECTIVES: The Global SFA Registry sought to assess safety, clinical benefit, and outcomes of the Lutonix 035 drug-coated balloon (DCB) in a heterogeneous, real-world patient population at 12 and 24 months. BACKGROUND: Numerous clinical studies have evaluated the use of angioplasty for revascularization of femoropopliteal arteries in peripheral arterial disease with restenosis rates of 40% to 60% at 6 to 12 months. Data from recent studies document decreased restenosis rates and improvement in patency in patients receiving angioplasty of femoropopliteal arteries with DCBs. METHODS: The multicenter, prospective study enrolled 691 patients in 38 centers from 10 countries treated with the Lutonix 035 DCB in femoropopliteal lesions. The primary safety endpoint was freedom from a composite of target vessel restenosis, major index limb amputation, and device- or procedure-related death at 30 days. The primary effectiveness endpoint was freedom from target lesion restenosis at 12 months. Secondary endpoints were acute device and procedural success and clinically assessed primary patency. RESULTS: Freedom at 30 days from the composite safety endpoint was 99.4%. Freedom from target lesion restenosis was 93.4%/89.3% for the overall population, 93.2%/88.2% for long lesions up to 500 mm, and 90.7%/84.6% for in-stent restenosis at 12/24 months. Clinically assessed primary patency by Kaplan-Meier estimates was 85.4%/75.6% at 12/24 months. More than 76% of patients showed improvement of at least 1 Rutherford category. CONCLUSIONS: The Global SFA Registry 24-month outcomes confirm the Lutonix 035 DCB is a safe and effective long-term treatment option in real-world patients with peripheral arterial disease with superficial femoral artery lesions, also in long lesions and in-stent restenosis. (Lutonix Global SFA Registry; NCT01864278).