One single drug-coated balloon for all shapes/diameters? Neointimal proliferation inhibition in porcine peripheral arteries.

BACKGROUND: Long diseased vessel segments of peripheral arteries may display irregular shapes with different diameters. The aim of this study was to investigate inhibition of neointimal proliferation in porcine peripheral vessels with different diameters covered by one single hyper-compliant drug-coated balloon (HCDCB), compared to conventional drug-coated balloons (DCB), each selected according to the respective vessel diameter. METHODS AND RESULTS: Neointimal proliferation was stimulated in proximal and distal segments of the peripheral arteries by balloon overstretch and stent implantation. Inhibition of neointimal proliferation by one single HCDCB was compared to two vessel diameter-adjusted DCB per artery and to one single uncoated hyper-compliant balloon (HCB). Sixteen HCB, 16 HCDCB, and 32 DCB were used in 16 arteries each. Quantitative angiography (QA), optical coherence tomography (OCT) and histology showed a similar anti-restenotic effect for one HCDCB compared to two vessel diameter-adjusted DCB in narrow distal and wider proximal segments (QA diameter stenosis: 18.7±12.3% vs. 22.8±15.5%, p = 0.535; OCT area stenosis: 21.4±11.6% vs. 23.6±12.3%, p = 0.850; histomorphometry diameter stenosis: 27.5±7.1% vs. 26.9±8.0%, p = 0.952) and indicated significant inhibition of neointimal proliferation by HCDCB vs. uncoated HCB (QA diameter stenosis: 18.7±12.3% vs. 30.3±16.7%, p = 0.008; OCT area stenosis: 21.4±11.6% vs. 34.7±16.0%, p = 0.004; histomorphometry diameter stenosis: 27.5±7.1% vs. 32.5±8.5%, p = 0.038). CONCLUSIONS: HCDCB were found to be similar effective as DCB in inhibiting neointimal proliferation in vessel segments with different diameters. One single long HCDCB may allow for treatment of segments with variable diameters, and thus, replace the use of several vessel diameter-adjusted DCB.

Drug-Coated Balloons: Drugs Beyond Paclitaxel?

BACKGROUND: Although controversially discussed, paclitaxel is the only clinically proven drug that inhibits restenosis when released from drug-coated balloons (DCBs). Limus drugs are currently being explored as alternatives. The aim of the preclinical studies was to investigate drug candidates beyond paclitaxel considered for balloon coating. METHODS: Drugs were tested with respect to dissolution in organic solvents, coating on balloons, and drug transfer to the vessel wall. Inhibition of neointimal proliferation was tested in the porcine model of coronary in-stent stenosis. Intravascular drug treatment was achieved by DCBs at the time of stent implantation. RESULTS: Coating had to be adjusted for each drug. Doses on the balloons ranged from 1.0 to 8.6 µg/mm2 balloon surface. Satisfactory amounts of drug ranging from 5% to 29% of initial doses were transferred into the vessel wall. Angiographic parameters such as late lumen loss (LLL) at 4 weeks did not show reduction of in-stent neointimal proliferation by treatment with arsenic trioxide (0.87 ± 0.44 mm), betamethasone dipropionate (1.00 ± 0.54 mm), bortezomib (1.74 ± 0.46 mm), green tea extract (1.24 ± 0.51 mm), fantolon, an epothilone (0.86 ± 0.61 mm), methotrexate (1.09 ± 0.72 mm), and thalidomide (1.59 ± 0.55 mm) compared to treatment with uncoated balloons (1.07 ± 0.60 mm), while coatings with paclitaxel reliably reduced in-stent stenosis (LLL = 0.36 ± 0.25 mm). CONCLUSIONS: Despite the proven antiproliferative and/or anti-inflammatory effect of the drugs, none of the coatings significantly reduced LLL compared to uncoated balloons and thus, based on the results presented here, none of the tested coatings may be considered a substitute for the paclitaxel-based coatings currently in clinical use.

Improvement of Outcome for Treatment of 'Restenosis-prone' Vascular Lesions? Potential Impact of the Paclitaxel dose on Late Lumen Loss in Porcine Peripheral Arteries.

PURPOSE: Clinical data indicate that the drug density on drug-coated balloons (DCBs) might have a role on treatment effect and durability. The aim of the current study was to investigate inhibition of neointimal formation and potential adverse effects after treatment with a novel double-dose DCB in swine. MATERIAL AND METHODS: A four-week study was performed in peripheral arteries of 12 domestic pigs after vessel injury and stent implantation. The novel double-dose DCB with 6-µg paclitaxel (Ptx)/mm2 balloon surface (1 × 6) was compared to a standard DCB with 3.5 µg Ptx/mm2 (3.5) and uncoated balloons (POBA). Potential adverse effects were stimulated by using three fully overlapping DCBs with 6 µg Ptx/mm2 each (3 × 6). Quantitative angiography, histomorphometry and histopathological analyses were performed. RESULTS: Higher paclitaxel doses per square millimeter of treated arteries were associated with reduced late lumen loss (LLL) in quantitative angiography 4 weeks after treatment (POBA: 0.91 ± 0.75 mm; 3.5: 0.45 ± 0.53 mm; 1 × 6: 0.21 ± 0.41 mm; 3 × 6: - 0.38 ± 0.65 mm). In histomorphometry, maximal neointimal thickness and neointimal area were the lowest for the 1 × 6 group (0.15 ± 0.06 mm/1.5 ± 0.4 mm2), followed by 3 × 6 (0.20 ± 0.07 mm/1.8 ± 0.4 mm2), 3.5 (0.22 ± 0.12 mm/2.2 ± 1.1 mm2) and POBA (0.30 ± 0.07 mm/3.2 ± 0.7 mm2). Downstream tissue showed histopathological changes in all groups including POBA, in larger number and different quality (e.g., edema, inflammation, vessel wall necrosis, vasculitis and perivasculitis) in the 3 × 6 group, which did not cause clinical or functional abnormalities throughout the study. CONCLUSION: Treatment with the double-dose DCB (6 µg Ptx/mm2) tended to increase inhibition of in-stent neointimal formation and to diminish LLL after peripheral intervention in the porcine model compared to a market-approved DCB with 3.5 µg Ptx/mm2.

Combined Analysis of Two Parallel Randomized Trials of Sirolimus-Coated and Paclitaxel-Coated Balloons in Coronary In-Stent Restenosis Lesions.

BACKGROUND: Paclitaxel-coated balloons (PCBs) are a preferred treatment option for coronary in-stent restenosis. To date, data from randomized trials of alternative drug coatings are lacking. The aim of the randomized Malaysian and German-Swiss randomized trials was to investigate a novel sirolimus-coated balloon (SCB) compared with a PCB in in-stent restenosis. METHODS: One hundred one patients with drug-eluting stent in-stent restenosis were enrolled in 2 identical randomized trials comparing the novel SCB (SeQuent SCB, 4 µg/mm²) with the clinically proven PCB (SeQuent Please, 3 µg/mm²). Primary end point was angiographic late lumen loss at 6 months. Secondary end points included procedural success, major adverse cardiac events, and individual clinical end points such as stent thrombosis, cardiac death, target lesion myocardial infarction, clinically driven target lesion revascularization, and binary restenosis. RESULTS: Quantitative coronary angiography revealed no differences in baseline parameters. After 6 months, in-segment late lumen loss was 0.25±0.57 mm in the PCB group versus 0.26±0.60 mm in the SCB group. Mean difference between SCB and PCB was 0.01 (95% CI, -0.23 to 0.24). Noninferiority at a predefined margin of 0.35 was shown. Clinical events up to 12 months did not differ between the groups. CONCLUSIONS: This first-in man comparison of a novel SCB with a crystalline coating showed similar angiographic and clinical outcomes in the treatment of coronary drug-eluting stent in-stent restenosis compared with PCB. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02996318, NCT03242096.

A novel paclitaxel coated balloon with increased drug transfer for treatment of complex vascular lesions.

BACKGROUND: Drug coated balloons (DCB) with paclitaxel (Ptx) dose of 2-3.5 µg/mm2 balloon surface inhibit restenosis with different effectiveness and duration of success. A clinical dose finding study is not known for any of the currently marketed products. The aim of the present preclinical trial was to investigate a novel DCB coated with 6 µg Ptx/mm2 in a porcine model. METHODS AND RESULTS: The current study investigated a DCB with a novel, modified iopromide based matrix with 6 µg Ptx/mm2. Drug transfer to the vessel wall of peripheral arteries was compared with a dose of 3 µg Ptx/mm2 and two fully overlapping DCB with 3 µg Ptx/mm2, each. Ptx concentration in the vessel wall after drug transfer was about twice as high for balloons with 6 µg/mm2 (1957±1472 µg/g) and two overlapping DCB with 3 µg Ptx/mm2, each (1287±619 µg/g) compared to a single balloon with 3 µg Ptx/mm2, (787±738 µg/g), with statistical significant differences for 1x6 µg/mm2 vs. 1x3 µg/mm2 (p = 0.017) but not for 2x3 µg/mm2 vs. 1x3 µg/mm2 (p = 0.184) and 1x6 µg/mm2 vs. 2x3 µg/mm2 (p = 0.178). The proportion of residual Ptx on balloon after treatment was similar for all groups between 6±1% and 10±3% of dose on balloon. CONCLUSION: The dose of 6 µg Ptx/mm2 was successfully as well as reproducibly coated on conventional balloon catheters. Increased Ptx on balloons resulted in increased drug concentration in the vessel wall. A single balloon with 6 µg Ptx/mm2 seems to provide double dose compared to 3 µg Ptx/mm2, facilitates the procedure, and may reduce medico-economic cost compared to the use of two standard DCB.

Preclinical Evaluation of the Temporary Drug-Coated Spur Stent System in Porcine Peripheral Arteries.

BACKGROUND: Drug penetration into the deeper arterial wall of heavily calcified lesions is one of the limitations of drug-coated balloons and drug-eluting stents in vascular interventions. The Temporary Spur Stent (TSS) system is characterized by a self-expanding nitinol stent that is uniformly covered in radialspikes, which, when coated, should allow a deeper penetration and longer retention of the drug into the diseased artery walls by penetrating through the calcified plaques. MATERIALS AND METHODS AND RESULTS: Uncoated TSS and paclitaxel (PTX)-coated TSS systems have been deployed in porcine peripheral arteries. Four weeks after the deployment of uncoated TSS systems, no adverse vascular remodeling or neointimal formation in the treated vessel segments were noticed. PTX-coated TSS systems transferred 9%±7% of the drug that was on the device to the targeted vessel area (196±163 ng PTX/mg arterial tissue) and the addition of the fluorescent dye Nile red to the coating showed that the spikes promote the transfer of the coating to the deeper layers of the vessel wall. The PTX-coated TSS systems showed a significant reduction in neointimal proliferation compared to the uncoated TSS systems: quantitative angiography showed a vessel diameter stenosis of 37.2%±11.0% and 16.4%±8.8% 4 weeks after the treatment with uncoated and PTX-coated TSS systems, respectively. CONCLUSION: The treatment with the TSS system was well tolerated and the spikesfacilitate the transfer of the coating into deeper layers of the vessel wall. Moreover, the PTX-coated TSS systems effectively inhibit neointimal proliferation.

Treatment of Coronary Drug-Eluting Stent Restenosis by a Sirolimus- or Paclitaxel-Coated Balloon.

OBJECTIVES: The aim of this randomized controlled trial was to investigate a novel sirolimus-coated balloon (SCB) compared with the best investigated paclitaxel-coated balloon (PCB). BACKGROUND: Treatment of coronary in-stent restenosis (ISR) remains challenging. PCBs are an established treatment option outside the United States with a Class I, Level of Evidence: A recommendation in the European guidelines. However, their efficacy is better in bare-metal stent (BMS) ISR compared with drug-eluting stent (DES) ISR. METHODS: Fifty patients with DES ISR were enrolled in a randomized, multicenter trial to compare a novel SCB (SeQuent SCB, 4 µg/mm2) with a clinically proven PCB (SeQuent Please Neo, 3 µg/mm2) in coronary DES ISR. The primary endpoint was angiographic late lumen loss at 6 months. Secondary endpoints included procedural success, major adverse cardiovascular events, and individual clinical endpoints such as stent thrombosis, cardiac death, target lesion myocardial infarction, clinically driven target lesion revascularization, and binary restenosis. RESULTS: Quantitative coronary angiography revealed no differences in baseline parameters. After 6 months, in-segment late lumen loss was 0.21 ± 0.54 mm in the PCB group versus 0.17 ± 0.55 mm in the SCB group (p = NS; per-protocol analysis). Clinical events up to 12 months also did not differ between the groups. CONCLUSIONS: This first-in-man comparison of a novel SCB with a crystalline coating shows similar angiographic outcomes in the treatment of coronary DES ISR compared with a clinically proven PCB. (Treatment of Coronary In-Stent Restenosis by a Sirolimus [Rapamycin] Coated Balloon or a Paclitaxel Coated Balloon [FIM LIMUS DCB]; NCT02996318).

Two-Year Mortality After Angioplasty of the Femoro-Popliteal Artery with Uncoated Balloons and Paclitaxel-Coated Balloons-A Pooled Analysis of Four Randomized Controlled Multicenter Trials.

PURPOSE: In view of a recent meta-analysis reporting increased mortality following angioplasty with paclitaxel-coated devices in peripheral arteries, we performed a patient-level 2-year mortality analysis based on pooled original data of four randomized controlled trials (THUNDER, FEMPAC, PACIFIER and CONSEQUENT). METHODS AND RESULTS: Clinical data of four randomized controlled trial were pooled to assess 2-year mortality following paclitaxel-coated balloon (PCB) angioplasty compared to angioplasty without paclitaxel (control group). A logistic regression model was applied to identify potential predictors of mortality. At two years, 13 of 185 (7.0%) patients had died in the control group and 16/184 (8.7%) in the PBC group, p = 0.55. Kaplan-Meier analysis revealed no significant difference from all-cause death at 2 years (log rank p = 0.54). Causes of death were well balanced between the groups with no pattern or trend in favour of any specific causes in the PBC group. Logistic regression revealed that treatment groups (controls or PBC) were not a predictor of 2-year mortality. The only predictor for mortality was patient age ≥ 75 years. The delivered paclitaxel doses per patient were not significantly different in patients that died and those who did not die during the 24-month follow-up (5.300 ± 4.224 µg vs. 6.248 ± 4.629 µg, p = 0.433). CONCLUSIONS: Based on original patient-level data of four pooled randomized controlled trials, we found no increase in 2-year mortality in patients treated with PCB compared to control patients treated with uncoated balloons. Causes of death were well balanced between PCB and control patients.

Angiographic and Clinical Outcomes After Treatment of Femoro-Popliteal Lesions with a Novel Paclitaxel-Matrix-Coated Balloon Catheter.

OBJECTIVES: Based on a novel paclitaxel-resveratrol drug matrix, the safety and efficacy to inhibit intimal hyperplasia were studied in symptomatic claudicants with morphologically challenging lesions. BACKGROUND: The treatment of peripheral artery occlusive disease (PAOD) with percutaneous transluminal angioplasty is limited by occurrence of vessel recoil and neointimal hyperplasia. Drug-coated balloons (DCB) deliver drugs to the arterial wall to potentially reduce the restenosis rate. A number of paclitaxel-coated balloon technologies are available to treat peripheral lesions. METHODS: In this randomized controlled trial, a total of 153 patients with symptomatic PAOD in femoro-popliteal lesions were randomized either to DCB or plain old balloon angioplasty (POBA). RESULTS: The mean lesion length was 13.2 ± 10.4 cm with target lesion total occlusions in 26.1% of all patients (40/153). The primary endpoint of in-lesion late lumen loss (LLL) at 6 months was significantly reduced in the DCB group as compared to the POBA group (0.35 mm CI [0.19; 0.79 mm] vs. 0.72 mm CI [0.68; 1.22 mm], p = 0.006). At 12 months, the TLR rate in the DCB group was significantly lower as compared to the POBA group (17.8 vs. 37.7% p = 0.008). The censored walking distance increase suggests a benefit for patients who underwent DCB angioplasty as compared to the standard POBA treatment (12 months 165 ± 105 vs. 94 ± 136 m, p = 0.012). CONCLUSION: The use of paclitaxel-resveratrol-matrix-coated peripheral balloon angioplasty as compared to POBA was associated with significantly reduced in-lesion LLL and reduced TLR rates. ClinicalTrials.gov identifier NCT01970579.

Angioplasty of femoral-popliteal arteries with drug-coated balloons: 5-year follow-up of the THUNDER trial.

OBJECTIVES: The purpose of this study was to evaluate the 5-year follow-up (FU) data of the THUNDER (Local Taxan With Short Time Contact for Reduction of Restenosis in Distal Arteries). BACKGROUND: The THUNDER trial was the first study to investigate the treatment of femoropopliteal arteries with a paclitaxel-coated balloon (PCB). METHODS: In 154 patients, femoropopliteal arteries were treated with PCB, with angioplasty with paclitaxel in contrast medium, or no paclitaxel (control). The primary endpoint was 6-month late lumen loss (LLL). Secondary endpoints included freedom from target lesion revascularization (TLR), binary restenosis rate, and amputation. The 5-year FU compares outcomes in patients treated with PCB and control subjects. Additionally, LLL at 6 months and TLR up to 5-year FU were analyzed in terms of sex and lesion length. RESULTS: Over the 5-year period, the cumulative number of patients with TLR remained significantly lower in the PCB group (21%) than in the control group (56%, p = 0.0005). In the small group of patients with angiographic and duplex sonographic follow-up, PCB was associated with a lower rate of binary restenosis (17% vs. 54%; p = 0.04). No signs of aneurysm formation or constrictive fibrosis were detected. Whereas LLL at 6-month FU did not differ between men and women in the PCB group, the TLR rate was lower in men than in women at 5-year FU. A benefit of PCB treatment in terms of LLL and TLR was seen independent of lesion length. CONCLUSIONS: The reduced TLR rate following PCB treatment was maintained over the 5-year FU period. No signs of drug-related local vessel abnormalities were detected. (Thunder Trial-Local Taxan With Short Time Contact for Reduction of Restenosis in Distal Arteries [THUNDER]; NCT00156624).

In vivo therapy monitoring of experimental rheumatoid arthritis in rats using near-infrared fluorescence imaging.

An in vivo near-infrared fluorescence (NIRF) imaging technique is described for therapy monitoring of ankle joints affected by collagen-induced arthritis, a model of human rheumatoid arthritis. Arthritis was induced in rats by intradermal injections of collagen and Freund's incomplete adjuvant. For in vivo imaging, the nonspecific NIR dye tetrasulfocyanine (TSC) was used. Prior to and after treatment with a nonsteroidal anti-inflammatory drug, meloxicam, or analgesic drug, tramadol hydrochloride (which served as no-therapy control), normalized fluorescence intensities of each ankle joint were measured. Additionally, each ankle joint was characterized by clinical arthritis scoring and histopathology. Over a 3-week treatment period, a significant difference in disease progression between animals treated with meloxicam and tramadol hydrochloride was detected. A statistically significant improvement in ankle joint pathology from high- or moderate-grade to moderate- or low-grade upon meloxicam therapy, as determined by clinical evaluation, translated into a significant decrease in fluorescence intensity. In contrast, all arthritic joints of the no-therapy control group deteriorated to high-grade arthritis with high-fluorescence intensities in NIRF imaging.

High-grade, non-flow-limiting dissections do not negatively impact long-term outcome after paclitaxel-coated balloon angioplasty: an additional analysis from the THUNDER study.

PURPOSE: To investigate the impact of using paclitaxel-coated balloons (PCB) on outcome after post-angioplasty dissection in femoropopliteal arteries. METHODS: The angiograms obtained in the THUNDER study (ClinicalTrials.gov identifier NCT00156624) were analyzed to compare degrees of dissection and angiographic parameters between the control (uncoated balloons, n=43) and treatment (PCBs, n=43) groups before and after the intervention and at 6-month follow-up. Furthermore, target lesion revascularizations (TLR) were documented up to 2 years. RESULTS: In each group, 24 (56%) patients had a dissection after the intervention. At the 6-month follow-up, patients with dissection of any grade after treatment with PCBs had significantly less late lumen loss (0.4 mm) than patients with dissection after treatment with uncoated balloons (1.9 mm, p=0.001) and a lower degree of stenosis (20% vs. 51%, respectively; p=0.003). Patients with severe dissection (grades C, D, or E) especially seemed to benefit from the PCBs, with late lumen loss of 0.4 mm vs. 2.4 mm for controls (p=0.05). The binary restenosis rate was also markedly lower in the PCB group (20%) than in the uncoated group (55%, p=0.02). In the 2-year follow-up, TLR was performed in 56% of patients in the control group compared to 10% of patients in the PCB group (p=0.002). CONCLUSION: The results of this subgroup analysis suggest that patients with dissection following treatment with a paclitaxel-coated balloon have a very acceptable outcome and stent implantation is not necessary as long as the dissection does not result in acute flow limitation.

Drug-coated balloons and their place in treating peripheral arterial disease.

Drug-coated balloons (DCB) have emerged as an additional treatment option for managing restenosis in lesions of the superficial femoral artery and of the infrapopliteal arterial bed. Relatively limited data are available on the use of DCB in these lesions, but scientific evidence is mounting. In five randomized controlled trials, late lumen loss 6 months after the intervention was found to be markedly lower in patients treated with paclitaxel-coated balloons (PCB) compared with uncoated balloons. Different types of PCB are currently on the market. It remains to be seen how different coatings affect the performance of PCB and clinical outcome. Long-term results are also awaited. In this review, the authors describe the components of DCB and how they affect performance. Then, the authors provide an overview of clinical results obtained with PCB in the superficial femoral artery and below the knee, and finally the article gives an outlook on the future of DCB in peripheral arterial disease.

Near-infrared fluorescence imaging of experimentally collagen-induced arthritis in rats using the nonspecific dye tetrasulfocyanine in comparison with gadolinium-based contrast-enhanced magnetic resonance imaging, histology, and clinical score.

Using 15 rats with collagen-induced arthritis (30 joints) and 7 control rats (14 joints), we correlated the intensity of near-infrared fluorescence (NIRF) of the nonspecific dye tetrasulfocyanine (TSC) with magnetic resonance imaging (MRI), histopathology, and clinical score. Fluorescence images were obtained in reflection geometry using a NIRF camera system. Normalized fluorescence intensity (INF) was determined after intravenous dye administration on different time points up to 120 min. Contrast-enhanced MRI using gadodiamide was performed after NIRF imaging. Analyses were performed in a blinded fashion. Histopathological and clinical scores were determined for each ankle joint. INF of moderate and high-grade arthritic joints were significantly higher (p<0.005) than the values of control and low-grade arthritic joints between 5 and 30 min after TSC-injection. This result correlated well with post-contrast MRI signal intensities at about 5 min after gadodiamide administration. Furthermore, INF and signal increase on contrast-enhanced MRI showed high correlation with clinical and histopathological scores. Sensitivities and specificities for detection of moderate and high-grade arthritic joints were slightly lower for NIRF imaging (89%/81%) than for MRI (100%/91%). NIRF imaging using TSC, which is characterized by slower plasma clearance compared to indocyanine green (ICG), has the potential to improve monitoring of inflamed joints.

Paclitaxel-coated balloons reduce restenosis after femoro-popliteal angioplasty: evidence from the randomized PACIFIER trial.

BACKGROUND: Peripheral percutaneous transluminal angioplasty is fraught with a substantial risk of restenosis and reintervention. A drug-eluting balloon (DEB) based on a novel coating was compared with uncoated balloons in patients undergoing femoro-popliteal percutaneous transluminal angioplasty. METHODS AND RESULTS: Patients with symptomatic femoro-popliteal atherosclerotic disease undergoing percutaneous transluminal angioplasty were randomized to paclitaxel-coated IN.PACT Pacific or uncoated Pacific balloons. The primary end point was late lumen loss at 6 months assessed by blinded angiographic corelab quantitative analyses. Secondary end points were binary restenosis and Rutherford class change at 6 months, and target lesion revascularization plus major adverse clinical events (major adverse events=death, target limb amputation, or target lesion revascularization) at 6 and 12 months. Eighty-five patients (91 cases=interventional procedures) were randomized in 3 hospitals (44 to DEB and 47 to uncoated balloons). Average lesion length was 7.0 ± 5.3 and 6.6 ± 5.5 cm for DEB and control arm, respectively. Procedural success was obtained in all cases. Six-month quantitative angiography showed that DEB were associated with significantly lower late lumen loss (-0.01 mm [95% CI, -0.29; 0.26] versus 0.65 mm [0.37; 0.93], P=0.001) and fewer binary restenoses (3 [8.6%] versus 11 [32.4%], P=0.01). This translated into a clinically relevant benefit with significantly fewer major adverse events for DEB versus uncoated balloons up to 12 months (3 [7.1%] versus 15 [34.9%], P<0.01) as well as target lesion revascularizations (3 [7.1%] versus 12 [27.9%], P=0.02). CONCLUSIONS: Use of IN.PACT Pacific DEB is associated with significant reductions in late lumen loss and restenoses at 6 months, and reinterventions after femoro-popliteal percutaneous transluminal angioplasty up to 1 year of follow-up. CLINICAL TRIAL REGISTRATION: URL http://www.clinicaltrials.gov. Unique identifier: NCT01083030.