Drug-eluting Balloon Group Research Articles

Balloon Coating with Rapamycin Using an On-site Coating Device

The efficacy of drug-eluting balloons has been demonstrated in clinical trials. The drug predominantly used is paclitaxel because of its lipophilic properties and the rapid onset of action. The aim of the investigation was to evaluate the feasibility and efficacy of an alternative balloon coating with rapamycin that can be applied on site. The balloon coating (3.0/18 and 3.0/12 mm, Cathy No. 4, Translumina GmbH) with rapamycin was conducted with a coating machine (Translumina GmbH). Concentrations were 2, 2 × 2, 3, and 4 %. Measurements regarding the amount of substance released to the vessel wall were carried out on explanted porcine coronaries by means of ultraviolet and visible-light spectroscopy. Inflation time varied between 30 and 120 s. The biological effect of the coating was evaluated in a porcine peripheral overstretch and stent implantation model. The amount of rapamycin on the balloon surface ranged from 558 ± 108 μg for the 2 % solution to 1,441 ± 228 μg in the 4 % solution. An amount of 95 ± 63-193 ± 113 μg was released into the vessel wall. The quantitative measurements of the angiographic examinations 4 weeks after treatment revealed a reduction of diameter stenosis from 20.6 ± 17.4 % in the control group to 11.6 ± 5.5 % in the drug-eluting balloon group. A balloon coating with rapamycin omitting an excipient is possible with a dose-adjustable coating machine. However, the biological effects are moderate, which make further optimization of the coating process and evaluation of appropriate excipients necessary.

Commentary: Drug-Eluting Balloons for Carotid In-Stent Restenosis: Can This Technology Deliver the Goods?

Percutaneous transluminal treatment of coronary and peripheral artery diseases has revolutionized the field of interventional medicine. Over the years, progressive technological and pharmacological advances have improved clinical outcome and offered an effective alternative to surgical treatment of atherosclerotic disease in both coronary and peripheral districts. Relatively new to this field are drug-eluting balloons (DEBs), which represent an attractive and novel treatment modality that offers numerous theoretical advantages over standard angioplasty and stent technologies. Among these benefits are homogenous distribution of an antiproliferative drug to the vessel wall (not just to segments of the wall in direct contact with stent struts); immediate drug release without the use of a polymer that could trigger late thrombosis; no prolonged, direct drug contact with the arterial wall, allowing better reendothelization of the vessel if a bare metal stent (BMS) is used in conjunction; no foreign object left in the body, which is especially important in peripheral applications where stents may be used for suboptimal results; maintenance of original vessel anatomy and flexibility, important during superficial femoral artery revascularization especially; and finally, lower restenosis rates in some indications. Recently, data from randomized clinical trials (RCT) showed that this technology is a viable alternative for the treatment of coronary in-stent restenosis (ISR) and of de novo and restenotic lesions in the peripheral arteries. Furthermore, treatment of bifurcation lesions, de novo lesions in small vessels, long lesions, and cerebrovascular interventions have been proposed. In the setting of ISR, the first major impact of DEBs in the management of ISR was shown by the results of the Paccocath ISR I trial (Treatment of In-Stent Restenosis by Paclitaxel Coated PTCA Balloons) comparing the efficacy of the Paccocath drug-eluting balloon vs. an uncoated balloon. The 6-month angiographic results showed binary restenosis and major adverse cardiovascular event (MACE) rates of 5% and 4%, respectively, in the DEB group compared with 43% and 31%, respectively, in the uncoated balloon group (p1⁄40.002 and 0.02). During a follow-up of 5.461.2 years, the clinical event rate was significantly reduced in patients treated with the DEB (59.3% vs. 27.8% MACE, p1⁄40.009), which was mainly driven by the reduction in target lesion revascularization (TLR) from 38.9% to 9.3% (p1⁄40.004).

A Randomized Multicenter Study Comparing a Paclitaxel Drug-Eluting Balloon With a Paclitaxel-Eluting Stent in Small Coronary Vessels: The BELLO (Balloon Elution and Late Loss Optimization) Study

The aim of this study was to evaluate the efficacy of drug-eluting balloons (DEB) compared with paclitaxel-eluting stents (PES) for the reduction of restenosis in small vessels. DEB have been shown to be effective in the treatment of coronary in-stent restenosis, but data are limited regarding their efficacy in de novo disease. BELLO (Balloon Elution and Late Loss Optimization) is a prospective, multicenter trial that randomized 182 patients with lesions located in small vessels (reference diameter <2.8 mm) to treatment with paclitaxel DEB and provisional bare-metal stenting (n = 90) or PES implantation (n = 92). The primary endpoint was noninferiority of angiographic in-stent (in-balloon) late loss with a delta of 0.25 mm. Secondary endpoints were angiographic restenosis, target lesion revascularization, and major adverse cardiac events (MACE; death, myocardial infarction, target vessel revascularization) at 6 months. Baseline characteristics were well matched, except for a smaller vessel size in the DEB group (2.15 ± 0.27 mm vs. 2.25 ± 0.24 mm; p = 0.003). The majority (89%) of lesions involved vessels with a diameter <2.5 mm. Bailout stenting was required in 20% of lesions in the DEB group. The primary endpoint of in-stent (in-balloon) late loss was significantly less with DEB compared with PES (0.08 ± 0.38 mm vs. 0.29 ± 0.44 mm; difference -0.21; 95% CI: -0.34 to -0.09; p(noninferiority) < 0.001; p(superiority) = 0.001). At 6 months, DEB and PES were associated with similar rates of angiographic restenosis (10% vs. 14.6%; p = 0.35), [corrected] target lesion revascularization (4.4% vs. 7.6%; p = 0.37), and MACE (10% vs. 16.3%; p = 0.21). [corrected]. Treatment of small-vessel disease with a paclitaxel DEB was associated with less angiographic late loss and similar rates of restenosis and revascularization as a PES. (Balloon Elution and Late Loss Optimization [BELLO]; Study NCT01086579).

Lower Limb Multilevel Treatment With Drug-Eluting Balloons:6-Month Results From the DEBELLUM Randomized Trial

To report 6-month results of the DEBELLUM (Drug-Eluting Balloon Evaluation for Lower Limb MUltilevel TreatMent) randomized trial to evaluate the efficacy of a drug-eluting balloon (DEB) to reduce restenosis after treatment of multilevel lower limb occlusive disease vs. a conventional angioplasty balloon (AB). Between September 2010 and March 2011, 50 consecutive patients (37 men; mean age 66±4 years) with 122 lesions (96 stenoses and 26 occlusions) of the femoropopliteal (92, 75.4%) or below-the-knee (BTK) arteries (30, 24.6%) were enrolled and randomly assigned to the DEB (25 patients with 57 lesions) or AB (25 patients with 65 lesions) group. Twenty patients presented multilevel lesions. Mean lesion length was 7.5±3.5 cm. Thirty-one (62%) of the patients were Fontaine stage IIb, while 19 (38%) were stage III or IV. DEBs or ABs were used for dilation of de novo lesions or for postdilation after primary stenting (superficial femoral artery only). Patients requiring provisional stenting after angioplasty secondary to flow-limiting dissection or residual stenosis >50% were ineligible. Primary endpoint was late lumen loss at 6 months. Secondary endpoints were target lesion revascularization (TLR), amputation, and thrombosis. Late lumen loss was lower in the DEB group (0.5±1.4 vs. 1.6±1.7 mm, p<0.01). TLR was necessary in 6.1% of the DEB group vs. 23.6% of the AB group (p=0.02). Comparing the DEB to AB groups, the thrombosis rates were 3.0% vs. 5.2% (p=0.6), and the amputation rates were 3.0% vs. 7.9% (p=0.36). The binary restenosis rates were 9.1% (3/33 limbs) in the DEB group vs. 28.9% (11/38 limbs) in the control group (p=0.03). The ankle-brachial index improved to a greater degree in the DEB group: 0.87±0.22 vs. 0.70±0.13 (p<0.05). The Fontaine stage improved in both groups but more so in patients treated with DEBs (p=0.04). The DEBELLUM trial confirmed the ability of paclitaxel-eluting balloons to reduce restenosis vs. conventional balloons at 6 months after treatment of multilevel (femoropopliteal and BTK) arterial disease in patients affected by claudication and CLI. A lower TLR rate and better clinical outcomes appear to be associated with the use of DEBs regardless of stent placement.

Preclinical evaluation of a novel drug-eluting balloon in an animal model of in-stent stenosis

Despite advances in contemporary stent technology, in-stent restenosis (ISR) remains the major limitation following revascularization procedures. We developed a porcine model of ISR to specifically investigate the preclinical outcomes of a novel drug-eluting balloon (DEB) in this particular setting. Fifteen pigs received bare metal stents in each of the major coronary arteries for 28 days to induce neointimal growth. Following repeat angiography, animals were allocated to fourdifferent treatment groups. The control group consisted of a bare angioplasty catheter, while the Pantera Lux™ (3.0 µg/mm(2) paclitaxel) (30 s inflation) was compared to two consecutive deployments of the Pantera Lux™ (60 s inflation each) and the commercial SeQuent(®) Please balloon (60 s inflation). Twenty-eight days following balloon deployment, the animals underwent repeat angiography and were subsequently sacrificed for histopathologic assessment. There was a trend in reduction of percent diameter stenosis in the DEB group versus control (13.9% vs. 20.4%), while longer inflation duration or consecutive DEB deployment had no additional growth-limiting effect. Neointimal thickness was reduced from 0.38 ± 0.13 to 0.30 ± 0.09 mm in the control versus DEB group. All DEB groups showed delayed vascular healing characterized by dose-dependent increases in fibrin deposition and neointimal cell vacuity. Investigation of DEB in a porcine model of ISR is feasible and more accurately represents human disease conditions. The magnitude of neointima suppression is lower than that observed in non-diseased animal models and is accompanied by delayed vascular healing.

In-stent restenosis: the gold standard has changed

In-stent restenosis remains an important issue even in the drug-eluting stent (DES) era today. In recent years, drug-eluting balloons (DEB) have emerged as a potential alternative to the treatment of in-stent restenosis. Paclitaxel was identified as the primary drug for DEB because of its rapid uptake and prolonged retention. Non-stent-based local drug delivery using DEB maintains the antiproliferation properties of DES, but without the limitations of DES such as subacute stent thrombosis, stent fractures, prolonged antiplatelet therapy and more importantly, avoiding a "stent-in-a-stent" approach. The first major impact of drug-eluting balloon (DEB) in the management of bare metal instent restenosis was the "PACCOCATH ISR I" randomised trial, comparing the efficacy of drug-eluting balloon versus uncoated balloon. The six months angiographic results showed a binary restenosis of 5% and 4% MACE in the drug-eluting balloon group, compared with 43% binary restenosis and 31% MACE, in the uncoated balloon group (p=0.002 and 0.02). The second major DEB trial is the "PEPCAD II Trial", comparing the efficacy of the SeQuent Please DEB with the Taxus drug-eluting stent in the treatment of bare-metal stent instent restenosis. At 6-month follow-up, in-segment late lumen loss was 0.38 ± 0.61 mm in the DES group versus 0.17 ± 0.42 mm (p=0.03) in the DEB group, resulting in a binary restenosis rate of 12/59 (20%) versus 4/57 (7%; p=0.06). At 12 months, MACE rates were 22% in the Taxus group and 9% in the DEB group (P=0.08). The TLR at 12 months was 15% in the Taxus group and 6% in the DEB group (p=0.15). Based on these two pivotal trials, the European Society of Cardiology Guidelines for Percutaneous Coronary Intervention (2010) recommended that DEB should be considered for the treatment of in-stent restenosis after prior bare-metal stent. This was accorded a class 2 IIa indication, with a level B evidence.

Comparative assessment of drug-eluting balloons in an advanced porcine model of coronary restenosis

The advent of drug-eluting balloon (DEB) therapy has represented an important development in interventional cardiology. Nevertheless, preclinical data with this technology remain scant, and comparative studies have not previously been published. Bare metal stents were implanted in the coronary arteries of 15 pigs followed by balloon angioplasty. Animals were allocated to treatment with a 60-second inflation of one of four different balloon catheters: a conventional untreated plain angioplasty balloon (PBA, Biotronik AG), the Pantera Lux DEB (3.0 μg/mm2 paclitaxel; BTHC excipient, Biotronik AG), the Elutax DEB (2.0 μg/mm2 paclitaxel; no excipient; Aachen Resonance), or the SeQuent Please DEB (3.0 μg/mm2 paclitaxel; iopromide excipient: B. Braun). Twenty-eight days following balloon deployment, animals underwent repeat angiography for quantitative coronary angiography analysis and euthanasia for histopathologic assessment. By histology, the mean neointimal thickness was 0.44 ± 0.19 mm with PBA, 0.35 ± 0.13 mm with Pantera Lux , 0.61 ± 0.20 mm with Elutax , and 0.47 ± 0.21 mm with SeQuent Please DEB (p=0.02). In comparison with PBA, deployment of the Pantera Lux or the SeQuent Please DEB resulted in delayed healing characterised by significant increases in fibrin, neointimal cell vacuity and delayed re-endothelialisation. In conclusion, investigation of comparative DEB performance in a porcine model of advanced coronary restenosis reveals significant heterogeneity of neointimal suppression between the devices tested with numerically lowest values seen in the Pantera Lux group. On the other hand, evidence of delayed healing was observed in the most effective DEB groups.