Uncoated Balloon Research Articles

Evaluation of mortality following paclitaxel drug-coated balloon angioplasty of femoropopliteal lesions in patients with ulcerations and gangrene - a single center experience.

Background: A recent meta-analysis of randomized controlled trials suggested an increased long-term mortality risk following femoropopliteal angioplasty using paclitaxel coated devices. To assess the long-term mortality after paclitaxel drug-coated (DCB) and uncoated balloon angioplasty (POBA) of femoropopliteal lesions in patients with ulcerations and gangrene in real world practice. Patients and methods: A retrospective mortality analysis of patients with at least 3-year follow-up who underwent balloon based endovascular therapy of femoropopliteal lesions was performed. Results: Overall 624 patients with femoropopliteal lesions were included in this study. Of those, 197 patients were treated with POBA without crossover to a paclitaxel coated device during follow-up and 427 patients with DCB angioplasty. Mean follow-up time was 33.3±25.4 months. Mortality incidence was 81.7% (95% confidence interval [95% CI]: 76.1-86.8) after POBA and 59.0% (95% CI: 54.6-63.9) after DCB (p<0.001). Multivariate logistic regression analysis revealed type of treatment (POBA vs. DCB, (hazard ratio [HR]: 0.332, 95% CI: 0.215-0.514, p<0.001), age per year (HR: 1.065, 95% CI: 1.046-1.087, p<0.001), coronary heart disease (HR: 1.969, 95% CI: 1.323-2.930, p=0.001), renal insufficiency (HR: 1.583, 95% CI: 1.079-2.323, p=0.019), stroke (HR: 2.505, 95% CI: 1.431-4.384, p=0.001) as predictors for all-cause mortality. In the subgroup excluding octogenarians, mortality predictors were type of treatment (HR: 0.463, 95% CI: 0.269-0.796, p=0.005), age per year (HR: 1.035, 95% CI: 1.002-1.069, p=0.038), coronary heart disease (HR: 2.082, 95% CI: 1.274-3.400, p=0.003), stroke (HR: 2.203, 95% CI: 1.156-4.197, p=0.016) and renal insufficiency (HR: 2.201, 95% CI: 1.357-3.571, p<0.001). Conclusions: This monocentric retrospective analysis showed no survival disadvantage for patients in Rutherford-Becker stage 5 after treatment with paclitaxel-coated balloons.

Propensity Score-Matched Analysis of Patients Treated With Paclitaxel-Coated Versus Uncoated Balloons

Paclitaxel (PTX)-coated balloons have been shown to decrease restenosis rates, but their use has been linked to a potential increase in late mortality. The purpose of this study was to examine 4-year outcomes after angioplasty with PTX compared with a matched control group treated without PTX. We retrospectively reviewed 1424 consecutive patients who underwent femoropopliteal artery intervention by angioplasty, atherectomy, stent placement, or combination between 2011 and 2019. Primary outcome measures were survival, amputation-free survival, freedom from major amputation, and freedom from target vessel revascularization (FF-TVR). Groups were divided into patients who received PTX and those who did not. Patients were propensity score matched 1:1 with respect to comorbidities and Rutherford class using a caliper width of 0.001 without replacement. Data were analyzed using Kaplan-Meier survival analysis, with log-rank P < .05 considered significant. Multivariable analyses used Cox proportional hazards. There were 1424 patients (PTX, n = 830; non-PTX, n = 594) who were propensity score matched, yielding 529 PTX and 529 non-PTX patients. After matching, all comorbidities were similar (P > .20), including presence of chronic limb-threatening ischemia (CLTI; 70.3% vs 67.1%; P = .29), diabetes (59.2% vs 58.2%; P = .80), chronic kidney disease (CKD; 36.3% vs 34.6%; P = .61), and smoking (72.4% vs 72.0%; P = .95). Through 4-year follow-up, patients in the PTX group demonstrated superior survival (Fig 1; 62.1% vs 51.8%; P = .04), amputation-free survival (Fig 2; 59.3% vs 46.4%; P = .0003), and freedom from major amputation (Fig 2; 91.3% vs 85.5%; P = .001). FF-TVR showed a benefit for PTX out to 3 years (year 1, 87.0% vs 80.2% [P = .003]; year 2, 81.4% vs 76.4% [P = .01]; year 3, 76.5% vs 74.8% [P = .047]). FF-TVR rates were similar at 4 years (73.6% vs 71.0%; P = .052). Multivariable Cox regression found that age, CLTI, CKD, diabetes, and hyperlipidemia were associated with mortality and that age, CLTI, CKD, and smoking history were associated with amputation. In a propensity score-matched analysis, patients treated with PTX achieved greater survival, amputation-free survival, and freedom from major amputation through 4-year follow-up than matched non-PTX patients. In addition, FF-TVR was higher in PTX patients until year 3 and became similar to that of non-PTX patients at year 4.Fig 2Kaplan-Meier survival analysis of freedom from major amputation (FF-Amp, gray lines) and amputation-free survival (AFS, black lines) based on the use of paclitaxel (PTX). SE, Standard error.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Comparative Study between Simple Percutaneous Transluminal Angioplasty and Drug-Coated Balloons in Chronic Total Occlusion of The Femoro-popliteal Artery

Background: Atherosclerotic peripheral artery disease (PAD) affects a growing number of patients in aging populations. Peripheral artery disease (PAD) accounts for a large proportion of cardiovascular disease (CVD) prevalence in most world regions. Objective: This study aims to evaluate and compare the patency, clinical outcome, and limb salvage rates between the simple percutaneous Transluminal angioplasty and the drug-coated balloons in chronic total occlusion of the femoropopliteal arterial segment on the short-term course. Patients and Method: A prospective randomized controlled comparative study was conducted in the vascular surgery department; Aswan University Hospital during the period from March 2018 to March 2020. In total, 30 patients with a well-established diagnosis of superficial femoral artery (SFA) and/or proximal popliteal lesions with symptoms of PAD. Results: The primary patency at 12-month following treatment with DCB was significantly better 100. %, 80.0%, 60.0% at 1, 6, 12 months compared with POBA 86.7 %, 66.7%, 46.7% at 1, 6, 12 months. The rate of clinically- driven TLR was the same in both groups (26.6%). The use of DCB was safe and did not increase the major adverse clinical events (death, myocardial infarction, and minor or major amputation) when compared with those seen with the use of the uncoated balloons). Conclusion: Use of DCBs is associated with improved vessel patency when compared to POBA in patients with FPD. There was no difference in clinically driven TLR between DCB and POBA in our study.

Comparative Study between Simple Percutaneous Transluminal Angioplasty and Drug-Coated Balloons in Chronic Total Occlusion of The Femoro-popliteal Artery

Background: Atherosclerotic peripheral artery disease (PAD) affects a growing number of patients in aging populations. Peripheral artery disease (PAD) accounts for a large proportion of cardiovascular disease (CVD) prevalence in most world regions. Objective: This study aims to evaluate and compare the patency, clinical outcome, and limb salvage rates between the simple percutaneous Transluminal angioplasty and the drug-coated balloons in chronic total occlusion of the femoropopliteal arterial segment on the short-term course. Patients and Method: A prospective randomized controlled comparative study was conducted in the vascular surgery department; Aswan University Hospital during the period from March 2018 to March 2020. In total, 30 patients with a well-established diagnosis of superficial femoral artery (SFA) and/or proximal popliteal lesions with symptoms of PAD. Results: The primary patency at 12-month following treatment with DCB was significantly better 100. %, 80.0%, 60.0% at 1, 6, 12 months compared with POBA 86.7 %, 66.7%, 46.7% at 1, 6, 12 months. The rate of clinically- driven TLR was the same in both groups (26.6%). The use of DCB was safe and did not increase the major adverse clinical events (death, myocardial infarction, and minor or major amputation) when compared with those seen with the use of the uncoated balloons). Conclusion: Use of DCBs is associated with improved vessel patency when compared to POBA in patients with FPD. There was no difference in clinically driven TLR between DCB and POBA in our study.

Comparison of efficacy and safety of drug-eluting versus uncoated balloon angioplasty for femoropopliteal arterial occlusive disease: a meta-analysis

BackgroundThis quantitative meta-analysis was conducted to evaluate the efficacy and safety of drug-eluting balloon (DEB) vs. uncoated balloon (UCB) in patients with femoropopliteal arterial occlusive disease.MethodsElectronic databases were searched to identify randomized controlled trials (RCTs) that compared DEB and UCB till November 2018. The random-effects model was used for conducting pooled analyses.ResultsSeventeen RCTs with 2706 patients were included in the final meta-analysis. Patients who received DEB had higher levels of minimal luminal diameter (MLD) at 6 (WMD: 0.77; 95%CI: 0.53 to 1.02; P < 0.001) and 12 months (WMD: 1.33; 95%CI: 0.93 to 1.73; P < 0.001) than those who received UCB. DEB reduced the late lumen loss (LLL) levels after 6 (WMD: -0.57; 95%CI: − 1.07 to − 0.06; P = 0.029) and 12 months (WMD: -0.95; 95%CI: − 1.28 to − 0.62; P < 0.001). DEB was found not superior over UCB on primary patency after 6 months (RR: 1.44; 95%CI: 0.88–2.35; P = 0.149), whereas DEB increased the primary patency after 12 (RR: 1.51; 95%CI: 1.25–1.83; P < 0.001) and 24 months (RR: 1.51; 95%CI: 1.30–1.77; P < 0.001). Patients who received DEB had reduced the risk of restenosis after 6 (RR: 0.47; 95%CI: 0.33–0.67; P < 0.001) and 12 months (RR: 0.55; 95%CI: 0.35–0.85; P = 0.008). DEB reduced the risk of major adverse events after 6 (RR: 0.30; 95%CI: 0.14–0.61; P = 0.001), 12 (RR: 0.49; 95%CI: 0.32–0.76; P = 0.001) and 24 months (RR: 0.62; 95%CI: 0.41–0.92; P = 0.018).ConclusionsDEB yielded additional benefits on MLD, LLL, primary patency, restenosis, TLR, and major adverse events than UCB in patients with femoropopliteal arterial occlusive disease.

Six-Month Outcomes From the First-in-Human, Single-Arm SELUTION Sustained-Limus-Release Drug-Eluting Balloon Trial in Femoropopliteal Lesions

Purpose: To evaluate the safety and efficacy of the novel SELUTION sustained-limus-release (SLR) drug-eluting balloon (DEB) in the treatment of femoropopliteal lesions. Materials and Methods: Between October 2016 and May 2017, 50 subjects (mean age 69.6±10.4 years; 29 men) with symptomatic moderate to severe lower limb ischemia (Rutherford categories 2 or 3) were enrolled at 4 German centers for the SELUTION SLR first-in-human trial (ClinicalTrials.gov NCT02941224). The SELUTION SLR utilizes micro-reservoirs (biodegradable polymer spheres containing sirolimus) embedded within an amphipathic membrane coated onto an angioplasty balloon. The biodegradable reservoirs are transferred to the target vessel lumen during brief balloon inflation. The primary trial objective was comparison of angiographic late lumen loss at 6 months against an objective performance criterion (OPC) value of 1.04 mm for uncoated balloon angioplasty. Secondary endpoints included device, procedural, and clinical success; clinical and imaging assessments of primary patency and restenosis; functional assessments including Rutherford category and ankle-brachial index (ABI); and major adverse events [composite of cardiovascular mortality, index limb amputation, target limb thrombosis, and clinically-driven target lesion revascularization (CD-TLR)]. Results: At 6 months, median angiographic late lumen loss following SELUTION SLR treatment was 0.19 mm (range −1.16 to 3.07). Mean angiographic late lumen loss (n=34) was 0.29±0.84 mm (95% CI −0.01 to 0.58), significantly lower than the 1.04-mm OPC value (p<0.001). The rate of primary patency by duplex ultrasound was 88.4%, and freedom from angiographic binary restenosis was 91.2%. Through 6 months, there was significant improvement over baseline in Rutherford categories (p<0.001) and in ABI measurements (p<0.001). A single case (2%) of CD-TLR occurred at 5 months. There were no other major adverse events. Conclusion: Through 6 months, the SELUTION SLR DEB appears to inhibit restenosis effectively and safely, improving outcomes in subjects with symptomatic femoropopliteal disease.

Clinical Outcomes Differ After Femoropopliteal Artery Treatment Between Individual Paclitaxel-Coated Balloons

Commercially available paclitaxel (PTX)-coated balloons (DCB) employ different PTX composition, PTX dose, and excipient. These balloons decrease restenosis compared to uncoated balloons (POBA), but not have been compared against each other. This study compares 4-year outcomes between patients treated with PTX-coated and POBAs.

A Propensity-Matched Analysis Demonstrates Lower Mortality and Major Amputation in Patients Treated With Paclitaxel-Coated Balloons Versus Uncoated Balloons

The use of paclitaxel (PTX)-coated balloons have been shown to decrease restenosis rates after intervention of the femoropopliteal artery. Recently, these devices have been linked to a potential increase in late mortality. The purpose of this study was to examine 4-year outcomes after PTX balloon treatment compared to a matched control group treated without PTX-coated devices.

Outcomes of Adjunctive Drug-Coated Versus Uncoated Balloon after Atherectomy in Femoropopliteal Artery Disease

The purpose of this study is to evaluate outcomes using drug-coated balloon (DCB) in comparison with uncoated balloon as adjunctive treatment after atherectomy for femoropopliteal artery lesions. This single-center retrospective and prospective study included 115 patients with 126 femoropopliteal artery lesions treated with endovascular treatment using atherectomy. Of these, 58 patients received adjunctive DCB after atherectomy (group A) and 57 patients were managed with uncoated balloon after atherectomy (group B). Immediate and late clinical outcomes were compared. Baseline clinical and lesion data were comparable between the 2 groups. However, group A included more uses of rotational atherectomy (43.9% vs. 1.7%, P<0.001) or embolization protection filter (53.0% vs. 6.7%, P=0.001), and fewer cases requiring provisional stenting (4.5% vs. 18.3%, P=0.014). Clinical primary patency at 1year was significantly higher in group A than in group B (76.3% vs. 61.1%, P=0.039). There was a trend toward higher 1-year target lesion revascularization (TLR)-free survival in group A (89.8% vs. 77.9% at 1year, P=0.275) without statistical significance. Proportional hazards regression analysis indicated that age (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.90-0.99, P=0.016) and provisional stenting (HR 9.78, 95% CI 2.20-43.46, P=0.003) were independent factors associated with restenosis after combined treatment with atherectomy and DCB. In femoropopliteal artery disease, the combination of atherectomy with adjunctive DCB achieved better clinical outcomes in terms of clinical primary patency compared to atherectomy plus uncoated balloon while TLR-free survival may also be improved.

Efficacy and safety of a novel paclitaxel-nano-coated balloon for femoropopliteal angioplasty: one-year results of the EffPac trial.

Although paclitaxel drug-coated balloon (DCB) angioplasty is an established endovascular treatment for peripheral artery disease, restenosis remains a major concern. Thus, we compared a novel paclitaxel-coated DCB with nano-coating technology with uncoated plain old balloon angioplasty (POBA). This multicentre trial randomly assigned 171 patients with stenotic and occlusive lesions of the femoropopliteal artery to angioplasty with a novel DCB or uncoated POBA. The primary endpoint, late lumen loss at six months, was 0.92 mm lower in the DCB group (95% CI: -1.36 to -0.49 mm, p<0.001). Patients showed improved walking after DCB treatment at six months (p=0.021). In the DCB group, 44.6% and 50% of the patients improved by three Rutherford-Becker classification stages after six to 12 months, respectively (POBA: 27.8% and 36.8%, respectively). Only one patient needed TLR (1.3%) in the DCB group, compared to 14 patients (18.7%) in the POBA group after 12 months (relative risk [RR]=0.08, 95% CI: 0.01-0.53, p<0.001). Primary patency was 90.3% (DCB group) versus 65.3% (POBA group) after 12 months (RR=1.38, 95% CI: 1.14-1.67, p<0.001). The novel DCB was effective and safe for inhibiting restenosis. Moreover, it demonstrated a better improvement in walking than POBA and showed no mortality concerns due to paclitaxel application after 12 months. Clinical Trials Identifier: NCT02540018

Pre-Clinical Investigation of Keratose as an Excipient of Drug Coated Balloons.

Background: Drug-coated balloons (DCBs), which deliver anti-proliferative drugs with the aid of excipients, have emerged as a new endovascular therapy for the treatment of peripheral arterial disease. In this study, we evaluated the use of keratose (KOS) as a novel DCB-coating excipient to deliver and retain paclitaxel. Methods: A custom coating method was developed to deposit KOS and paclitaxel on uncoated angioplasty balloons. The retention of the KOS-paclitaxel coating, in comparison to a commercially available DCB, was evaluated using a novel vascular-motion simulating ex vivo flow model at 1 h and 3 days. Additionally, the locoregional biological response of the KOS-paclitaxel coating was evaluated in a rabbit ilio-femoral injury model at 14 days. Results: The KOS coating exhibited greater retention of the paclitaxel at 3 days under pulsatile conditions with vascular motion as compared to the commercially available DCB (14.89 ± 4.12 ng/mg vs. 0.60 ± 0.26 ng/mg, p = 0.018). Histological analysis of the KOS–paclitaxel-treated arteries demonstrated a significant reduction in neointimal thickness as compared to the uncoated balloons, KOS-only balloon and paclitaxel-only balloon. Conclusions: The ability to enhance drug delivery and retention in targeted arterial segments can ultimately improve clinical peripheral endovascular outcomes.

Paclitaxel-Coated Balloon vs Uncoated Balloon Angioplasty for Treatment of In-Stent Restenosis in the Superficial Femoral and Popliteal Arteries: The COPA CABANA Trial

Purpose: To investigate the efficacy and sustainability of drug-coated balloon (DCB) treatment of femoropopliteal in-stent restenosis (ISR). Materials and Methods: An investigator-initiated, prospective, multicenter, 1:1 randomized study enrolled 88 patients for treatment of ISR with DCB (n=47; mean age 68.3±9.6 years; 26 men) or uncoated balloon (n=41; mean age 67.6±10.2 years; 26 men) angioplasty (ClinicalTrials.gov identifier NCT01594684). Additionally, the protocol provided for an observational arm composed of patients from either randomized arm who experienced recurrent ISR ≥30 days after the index treatment. Redo treatment consisted of 2 DCBs sequentially inflated at the same location (double dose therapy). The majority of patients (66, 78%) had Rutherford category 3 ischemia. The mean lesion length was 140 mm; a third (27, 31%) were total occlusions. The primary endpoint was angiographic late lumen loss (LLL) at 6 months evaluated by an independent core laboratory. Results: Twenty-two patients (7 DCB +15 uncoated) were treated for recurrence with fully overlapping double DCB angioplasty. Six-month LLL was lower after DCB (0.34±1.12 mm) treatment than after angioplasty with an uncoated balloon (1.58±1.10 mm, p<0.001). At the 12-month follow-up, target lesion revascularization (TLR) was performed in 18 (49%) of 37 patients in the uncoated group, 6 (14%) of 43 patients in the single-dose DCB group (p=0.001), and no patients from the recurrent ISR group. At ~2 years after treatment, a remarkable number (14/27, 52%) of TLRs were recorded in the single-dose DCB group. Conclusion: Treatment with DCBs resulted in significantly less 6-month LLL and fewer TLRs up to 24 months than treatment with uncoated balloons. The double dose for treating recurrent ISR did not cause recognizable adverse events or require TLR up to 24 months.

How does drug-eluting angioplasty compare with uncoated balloon angioplasty for adults with in-stent restenosis of femoropopliteal arteries?

How does drug-eluting angioplasty compare with uncoated balloon angioplasty for adults with in-stent restenosis of femoropopliteal arteries?

Risk of Death and Amputation with Use of Paclitaxel-Coated Balloons in the Infrapopliteal Arteries for Treatment of Critical Limb Ischemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

A formal systematic review and study-level meta-analysis of randomized controlled trials investigating treatment of the infrapopliteal arteries with paclitaxel-coated balloons compared with conventional balloon angioplasty for critical limb ischemia (CLI) was conducted. Medical databases and online content were last screened in September 2019. The primary safety and efficacy endpoint was amputation-free survival defined as freedom from all-cause death and major amputation. Target lesion revascularization (TLR) constituted a secondary efficacy endpoint. Summary effects were synthesized with a random-effects model. Some 8 randomized controlled trials with 1,420 patients (97% CLI) were analyzed up to 1 year follow-up. Amputation-free survival was significantly worse in case of paclitaxel (13.7% crude risk of death or limb loss compared to 9.4% in case of uncoated balloon angioplasty; hazard ratio 1.52; 95% confidence interval: 1.12-2.07, p = .008). TLR was significantly reduced in case of paclitaxel (11.8% crude risk of TLR versus 25.6% in control; risk ratio 0.53; 95% confidence interval: 0.35-0.81, p = .004). The harm signal was evident when examining the high-dose (3.0-3.5μg/mm2) devices, but attenuated below significance in case of a low-dose (2.0 μg/mm2) device. Actual causes remain largely unknown, but non-target paclitaxel embolization is a plausible mechanism.

Major Adverse Limb Events in Patients With Femoro-popliteal and Below-the-knee Peripheral Arterial Disease Treated With Either Sirolimus-coated Balloon or Standard Uncoated Balloon Angioplasty

Major Adverse Limb Events in Patients With Femoro-popliteal and Below-the-knee Peripheral Arterial Disease Treated With Either Sirolimus-coated Balloon or Standard Uncoated Balloon Angioplasty

Drug-coated vs uncoated balloon angioplasty in the treatment of femoropopliteal arterial lesions

Background Inspite of immediate technical success, neointimal hyperplasia and restenosis remain the Achilles heel of endovascular interventions. Drug-coated balloons (DCBs) have shown promising outcomes regarding anti-restenotic efficacy in management of femoro-popliteal arterial lesions compared to uncoated balloon. Objectives To evaluate the efficacy of the paclitaxel-coated balloon versus uncoated balloon angioplasty in treatment of femoropopliteal lesions regarding primary patency and restenosis at 12 months. Patients and Methods Between Sept 2017 and Sept 2019, this prospective randomized study was performed at Menoufia University hospitals. Sixty patients suffering symptomatic lower limb ischemia (Rutherford category 3 to 5) were randomly assigned into group A (30 patients) that were treated by DCB angioplasty, and group B (30 patients) that were treated by uncoated balloon (UCB) angioplasty. The primary patency, mean diameter restenosis, and binary restenosis (≥50% diameter stenosis) of the treated lesions at 12 months were collected and analyzed. Results Baseline characteristics were comparable in both groups. The 12-month mean diameter restenosis was significantly lower in DCB group than UCB group (27.8±35.2% vs. 44.9±33.8% respectively, P Conclusions Treatment of symptomatic femoro-popliteal disease with paclitaxel coated balloon angioplasty is associated with superior anti-restenotic efficacy that provides a better primary patency rate compared to uncoated balloon angioplasty at 12 months.

Novel, vessel anatomy adjusting drug-coated balloon-Preclinical evaluation in peripheral porcine arteries.

The diameter of balloons or stents is selected according to the estimated reference vessel diameter and do not adapt to the vessel anatomy. The aim of the present preclinical studies was to investigate a novel, vessel anatomy adjusting hypercompliant drug-coated balloon catheter (HCDCB). Hypercompliant balloon membranes were coated in a constricted state with high drug density. Drug adherence was investigated in vitro, transfer to the porcine peripheral arteries and longitudinal distribution in vivo. In young domestic swine, neointimal proliferation was induced by vessel overstretch and continuous irritation by permanent stents. Uncoated hypercompliant balloons (HCB), and standard uncoated balloons and drug-coated balloons (DCB) served as controls. Efficacy was assessed by angiography, optical coherence tomography (OCT), and histomorphometry. HCDCB lost 18.0 ± 3.9% of dose during in vitro simulated delivery to the lesion. Drug transfer to the vessel wall was 13.9 ± 6.4% and drug concentration was 1,044 ± 529 ng/mg tissue. Four weeks after treatment, the histomorphometric neointimal area was smaller with HCDCB versus uncoated HCB (2.39 ± 0.55 mm2 vs. 3.26 ± 0.72 mm2 , p = .038) and area stenosis (OCT) was less (11.6 ± 6.9% vs. 24.7 ± 9.7%, p = .022). No premature death occurred and no in-life clinical symptoms or treatment-associated thrombi were observed. HCDCB were found to inhibit excessive neointimal proliferation. Balloon adaption to different vessel diameters and shapes may provide drug-delivery in irregular lumen and facilitate balloon selection.

Mortality after use of paclitaxel-based devices in peripheral arteries: a real-world safety analysis.

AimsDrug-eluting devices (DED) represent a well-established therapy being widely used for endovascular revascularization (EVR) of peripheral vessels. Recent data indicate a two-fold increased long-term mortality in patients treated with paclitaxel-based DED. The subsequent safety concerns affected international regulatory authorities to enunciate several alerts for further application of DED.Methods and resultsIn 9.2 million insurants of the German BARMER Health Insurance, data on the application of paclitaxel-based drug-eluting stents (DES) and drug-coated balloons (DCB) were retrieved from their introduction on the market in 2007 until present. All patients with first EVR between 2007 and 2015 were indexed and followed until 31 December 2017. Each subsequently applied DES, DCB, bare-metal stent, and uncoated balloon was included in further analyses. Multivariable Cox regression analysis considered potential non-linear time-dependent hazard ratios (HRs) of DES and DCB over 11 years. We identified 64 771 patients who underwent 107 112 EVR procedures using 23 137 DED. Multivariable Cox regression analysis showed paclitaxel-based DES not to be associated with increased long-term mortality for over 11 years past application (all P > 0.057). DCB was associated with decreased long-term mortality for the first year past application (HR 0.92; P < 0.001), and indifferent correlation in the years thereafter (all P > 0.202).ConclusionOur real-world analysis showed no evidence for increased mortality associated with paclitaxel-based DED for over 11 years.

Safety of Paclitaxel-Coated Balloon Angioplasty for Femoropopliteal Peripheral Artery Disease

ObjectivesThe aim of this study was to assess safety outcomes of femoropopliteal drug-coated balloon (DCB) angioplasty using patient-level data from the Lutonix clinical program. BackgroundA recent systematic review and meta-analysis of heterogenous trials and summary-level data identified increased long-term mortality in patients treated with paclitaxel-coated balloons and stents. MethodsWe evaluated DCB angioplasty (n = 1,093) and uncoated balloon angioplasty (percutaneous transluminal angioplasty [PTA]) (n = 250) outcomes in LEVANT 1 (The Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis), LEVANT 2 (Moxy Drug Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Femoropopliteal Arteries), and the LEVANT Japan Clinical Trial. Hazard ratios (HRs) were calculated with Cox proportional hazards modeling. ResultsThere were no significant differences in mortality rates between DCB angioplasty and PTA. The 5-year HR was 1.01 (95% confidence interval [CI]: 0.68 to 1.52) in the aggregated LEVANT trials. The 2-year HR after DCB angioplasty was 0.99 (95% CI: 0.25 to 3.95) in LEVANT 1, 1.40 (95% CI: 0.62 to 3.14) in LEVANT 2, and 0.32 (95% CI: 0.05 to 1.92) in the LEVANT Japan Clinical Trial. The 5-year HR was 1.60 (95% CI: 0.94 to 2.72) in LEVANT 2. Adverse events and causes of death were balanced, without clustering between DCB angioplasty and PTA. Patients who underwent paclitaxel or nonpaclitaxel reinterventions had higher survival rates than those who did not undergo reinterventions. Baseline covariates predicting mortality included, among others, age (HR: 1.03 per year; p < 0.0001), prior treatment of target lesion (HR: 1.67; p = 0.022), arrhythmia (HR: 1.65; p = 0.031), and diabetes (HR: 1.18; p = 0.047), without differences between the 2 arms. No dose-response relationship was identified when adjusted for key predictors of mortality. ConclusionsAnalyses of patient-level data identified no mortality differences between DCB angioplasty and PTA. Furthermore, the lack of dose-response relationships or clustering of causes of death argues against a causal relationship between paclitaxel and mortality. (LEVANT 1, The Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis [LEVANT 1], NCT00930813; Moxy Drug Coated Balloon vs. Standard Balloon Angioplasty for the Treatment of Femoropopliteal Arteries [LEVANT 2], NCT01412541; LEVANT 2 Continued Access Registry, NCT01628159; LEVANT Japan Clinical Trial, NCT01816412)

Mortality After Paclitaxel-Coated Device Use in Dialysis Access: A Systematic Review and Meta-Analysis

Purpose: To report the risk of all-cause mortality in patients who underwent dialysis access treatment using paclitaxel-coated devices compared with percutaneous transluminal angioplasty (PTA) with an uncoated balloon. Materials and Methods: A systematic review and meta-analysis of randomized controlled trials were performed to investigate the mortality outcomes associated with paclitaxel-coated devices in the treatment of patients with a failing dialysis access (last search date February 28, 2019). The primary endpoint was all-cause mortality. This analysis included 8 studies comparing paclitaxel-coated balloon (PCB) angioplasty (n=327) and PTA (n=331) in the treatment of failing dialysis access. None investigated paclitaxel-coated stents. Mortality data were pooled using a random effects model. Statistical heterogeneity was evaluated with a chi-square test and the I2 statistic. Summary statistics are expressed as relative risk ratios (RR) with a 95% confidence interval (CI). Results: At the pooled mean follow-up of 13.5 months (median 12, range 6–24) all-cause mortality was similar in the PCB group (13.8%) compared with PTA (11.2%; RR 1.26, 95% CI 0.85 to 1.89, p=0.25; I2=0%). Subgroup analysis, stratified according to length of follow-up, confirmed that there were no statistically significant differences in mortality at short- and midterm follow-up [6-month (8 studies): 5.2% vs 4.8%, RR 1.24, 95% CI 0.62 to 2.47, p=0.55; 12-month (6 studies): 6.3% vs 6.0%, RR 1.06, 95% CI 0.43 to 2.63, p=0.90; and 24-month (3 studies): 19.0% vs 13.5%, RR 1.38, 95% CI 0.90 to 2.12, p=0.14). Conclusion: The analysis found no difference in short- to midterm mortality among patients treated with a drug-coated balloon compared with PTA. With proven benefit and no evidence of harm, the authors recommend ongoing use of PCB for the failing dialysis access.