Drug-coated Balloon Technology Research Articles

药物涂层球囊技术治疗冠脉病变研究进展

药物涂层球囊技术治疗冠脉病变研究进展

Is Coronary Brachytherapy Staging a Comeback for the Treatment of In-Stent Restenosis?

The catheter-based coronary intervention has become a well-established therapeutic modality for obstructive coronary artery disease. However, in-stent restenosis remains a significant limitation of coronary intervention despite the use of newer devices. Intravascular brachytherapy was introduced to treat recurrent in-stent restenosis but only modestly adopted. This review will discuss the mechanism of intracoronary brachytherapy, available clinical evidence of brachytherapy in recurrent in-stent restenosis treatment, and the future of coronary brachytherapy in coronary intervention. Drug-eluting stents have an inherent limitation as they leave a permanent metal layer inside an artery when deployed. Recently, drug-coated balloon technology has emerged to treat coronary artery disease as a combination of balloon angioplasty and local drug delivery without leaving a metal layer behind. Recent European guidelines recommended using drug-coated balloons when treating in-stent restenosis treatment, while the US guidelines have not yet addressed the use of drug-coated balloons in such cases. Coronary brachytherapy is a valuable addition to treat these challenging diseases despite several logistic issues. If there are newer technologies with easier setup, such as drug-coated balloons, coronary brachytherapy resurgence is improbable in the contemporary era, although it may not become obsolete.

Progress on developing an effective below-the-knee drug-coated balloon.

Infrapopliteal atherosclerotic disease continues to present the greatest conundrum for effective endovascular therapies. To date, conventional angioplasty has been fraught with early restenosis and recoil in these complex, long, calcified, and occlusive lesions. The success of metallic drug-eluting stents in coronary arteries has not carried over to below-the-knee arteries. Initial promise in paclitaxel-coated balloons has not been demonstrated in large randomized clinical trials. Furthermore, the potential association between paclitaxel and mortality continues to generate tremendous controversy. The goal of this review article is to discuss the evolution and challenges of drug-coated balloon (DCB) science, present the clinical results of currently available tibial DCBs, and introduce new horizons in DCB technology.

Propensity Score Matched Analysis Indicated That Insulin-dependent Diabetic Patients have More Benefit of Drug Coated Balloon Angioplasty in the Treatment of Chronic Limb Threatening Ischemia

Introduction - There is an increasing evidence on efficacy of drug coated balloons(DCB) in reducing restenosis and reocclusion after endovascular treatment of peripheral arterial disease(PAD), especially in the femoro-popliteal district but DCB use is discouraged by its high cost. The aim of the study was to identify subgroups of patients with chronic limb threatening ischemia (CLTI) that can benefit more from DCB than others and thus, perform a better resources management. Methods - A propensity score matched analysis was performed on a prospectively maintained database, including all patients treated for PAD between January-2014 and December-2017. Inclusion criteria were: CLTI, infrainguinal PAD and endovascular treatment. Patient's demographics and clinical characteristics were assessed. Limbs were stratified according to WIfI clinical stages. Clinical and Duplex follow-up was performed at 3,6 and every 6 month thereafter. A propensity score analysis was used to match all DCB treated patients to balloon angioplasty(BA) patients in a 1:1 nearest neighbour matching method. The matching variables were: age, diabetes, Rutherford stage, treated arterial segment (femoral, tibial and femoro-tibial) and type of lesion (primary vs. restenosis/reocclusion). Endpoints were: Limb Salvage(LS), Primary(PP), Assisted(AP) and Secondary Patency(SP), Patient Survival(S), wound healing (WH) and identification of subgroups susceptible to DCB on the basis of Kaplan-Meier analysis and Log-Rank test. Results - A total of 211 patients satisfying the inclusion criteria were treated in the study period. DCB was used in 60 cases (median age 72 years, male 76.7%). Sixty (median age 73 years, male 66.7%) out of 151 cases treated by POBA were selected, based on the propensity score matching. DCB and POBA groups were similar in terms of Coronary artery disease (47% Vs 50%. P=0.43), insulin-dependent diabetes(IDD) (40% Vs 27%. P=0.09), kidney disease (45% Vs 60%. P=0.07), Rutherford stages 5/6 (87% Vs 88%. P=0.41), and WIfI clinical stages (stage 3: 37% Vs 42%; stage 4: 31% Vs 27%; P=0.92). In the overall population, femoral, tibial and femoro-tibial lesions were treated in 44%, 49% and 7%, respectively. Lesion type was primary in 73% and restenosis/reocclusion in 27%. The mean follow-up was 21.5 months. WH was 54%, 75% and 85.7% at 6,12 and 24-month, respectively. LS was 87.2%, 86.1% and 84.7% at 6,12 and 24-month, respectively. PP, AP, SP, and S are reported in table 1. At Cox-regression analysis, IDD was an independent negative predictor of LS (HR=3.4, P=0.011). Within IDD patients, at 1-year, those treated by DCB had significantly higher rates of LS (81.1% Vs 56.3%, P=0.05), AP (80% Vs 50%, P=0.04) and SP (85% Vs 56%, P=0.029).Table 1endpoints at 6,12 and 24-monthPP (%)AP (%)SP (%)S (%)6-month8081.885.389.812-month73.575.183.185.624-month6872.481.174.6 Open table in a new tab Conclusion - The study results suggest a more beneficial effect of DCB in the treatment of infrainguinal PAD associated with CLTI in insulin-dependent diabetes patients. In a limited resources assets, insulin-dependent patients could represent a reasonable target for DCB technology.

Current evidence of drug-elution therapy for infrapopliteal arterial disease

New and sophisticated endovascular devices, such as drug-eluting stents (DES) and drug-coated balloons (DCB), provide targeted drug delivery to affected vessels. The invention of these devices has made it possible to address the reparative cascade of arterial wall injury following balloon angioplasty that results in restenosis. DESs were first used for the treatment of infrapopliteal lesions almost 20 years ago. More recently, however, DCB technology is being investigated to improve outcomes of endovascular below-the-knee arterial procedures, avoiding the need for a metallic scaffold. Today, level IA evidence supports the use of infrapopliteal DES for short to medium length lesions, although robust evidence that justifies the use of DCBs in this anatomical area is missing. This review summarizes and discusses all available data on infrapopliteal drug-elution devices and highlights the most promising future perspectives.

Atherectomy plus antirestenotic therapy for SFA lesions: evolving evidence for better patency rates in complex lesions.

Within the last years, many new endovascular treatment modalities have been invented for treatment of peripheral arterial disease. To leave nothing behind and to keep options for future treatment are key issues of these new revascularization procedures. Drug coated balloon technology (DCB) is one key element in this strategy but there are still limitations for this revascularization technology. Especially calcium rich lesions and long lesions are still challenging in terms of treatment success and long-term patency. Treatment of both calcified and long lesions continues to be a clinical challenge for every interventionalists. Therefore, a treatment combination of debulking procedure using atherectomy plus antirestenotic therapy using DCB seems to be promising to treat complex lesions.

What are the Pathological Concerns and Limitations of Current Drug-coated Balloon Technology?

The use of endovascular therapy for peripheral artery disease and coronary artery disease has increased and spread worldwide and is considered as the foremost, guideline-based invasive treatment. Drug-coated balloons (DCBs) utilise anti-proliferative drugs similar to drug-eluting stents; however, the do not leave any permanent metallic scaffold. Excipients and drug formulations play a crucial role in innovative DCB technologies and allow for treatment of lesions where stents are not suitable. Although the significance of downstream embolic effects after DCB use remains uncertain, several preclinical studies suggest such side effects might pose safety concerns. Recently, a meta-analysis of randomised controlled trials of paclitaxel devices suggested an association between increased mortality and paclitaxel device use. Subsequently, unfavourable criticism of paclitaxel devices attracted much attention and gave rise to a discussion about the safety of such devices. In this review, we will focus on the novel DCB technologies from the standpoint of preclinical studies and clinical trials, as well as discuss current controversies regarding the increase in death rates from paclitaxel-coated DCBs versus control devices seen in a recent meta-analysis of randomised controlled clinical trials.

IVUS guidance can optimise DCB treatment in the SFA

Aim Drug-coated balloon (DCB) angioplasty is a common endovascular treatment that has lower rates of restenosis compared to plain angioplasty. Restenosis rates remain higher than is desirable even with the use of DCB technology. This study was undertaken to investigate whether guidance using IVUS resulted in lower rates of restenosis. Methods A subgroup of patients who undergone primary treatment with DCB and had one year follow-up available was extracted from cases enrolled in an on-going RCT investigating the use of IVUS guidance in femoropopliteal endovascular interventions. Patient, lesion and procedural parameters were compared between the treatment group (who had IVUS and angiographic guidance) and the control group (only angiography guidance). The rate of binary restenosis was compared between the two groups. Results A total of 76 patients had treatment by DCB (36 in control group and 40 in treatment group). There was no difference in parameters between the two groups. There was a significantly higher rate of binary restenosis at one year in the control group compared to the treatment group (47% v 15%, p=0.003). Median balloon size was significantly larger in the treatment group than the control group (6 mm v 5 mm, p=0.019). The median difference between the angiographic measurement and the actual treated length was significantly greater in the treatment group compared to the control group (40 v. 0 mm), p=0.010. Conclusion These findings suggest that the reduced rate of restenosis rates found when IVUS guidance was used may be due to optimised drug delivery during DCB treatment by improved matching of the DCB to the vessel lumen dimensions and better coverage of the true lesion length.

TCT-525 First Report of the 12-Month Outcomes of SELUTION Trial: A Novel Sirolimus Coated DCB Technology Evaluated in SFA

Most Drug Coated Balloons (DCB) typically transfer drugs with an excipient to the vessel wall during balloon expansion within minutes. By inventing a new technology sirolimus containing PLGA microspheres were attached to a balloon surface within a phospholipid transfer membrane. Upon balloon

Endovascular Therapy of Axillary Artery Disease with Drug-Coated Balloon Angioplasty

The occurrence of upper-extremity arterial disease is less common than that of the lower extremities. Nevertheless, exercise-induced symptoms, when present, can significantly affect functional capacity and limit quality of life. We report a case of exertional right upper-extremity pain and severe right axillary artery disease that was revascularized using an off-label drug-coated balloon technology with resolution of symptoms.

Critical appraisal of paclitaxel balloon angioplasty for femoral-popliteal arterial disease.

Peripheral arterial disease, particularly critical limb ischemia, is an area with urgent need for optimized therapies because, to date, vascular interventions often have limited life spans. In spite of initial encouraging technical success after femoropopliteal percutaneous transluminal angioplasty or stenting, postprocedural restenosis remains the major problem. The challenging idea behind the drug-coated balloon (DCB) concept is the biological modification of the injury response after balloon dilatation. Antiproliferative drugs administered via DCBs or drug-eluting stents are able to suppress neointimal hyperplasia, the main cause of restenosis. This article reviews the results of DCB treatments of femoropopliteal and infrapopliteal lesions in comparison to standard angioplasty with uncoated balloons. A systematic literature search was performed in 1) medical journals (ie, MEDLINE), 2) international registers for clinical studies (ie, www.clinicaltrials.gov), and 3) abstracts of scientific sessions. Several controlled randomized trials with follow-up periods of up to 5 years demonstrated the efficacy of paclitaxel –DCB technology. However, calcified lesions seem to affect the efficacy of DCB. Combinations of preconditioning methods with DCBs showed promising results. Although the mechanical abrasion of calcium via atherectomy or laser ablation showed favorable periprocedural results, the long-term impact on restenosis and clinical outcome has to be demonstrated. Major advantages of the DCBs are the rapid delivery of drug at uniform concentrations with a single dose, their efficacy in areas wherein stents have been contraindicated until now (ie, bifurcation, ostial lesions), and in leaving no stent scaffold behind. Reinterventions are easier to perform because DCBs leave no metal behind. Various combinations of DCBs with other treatment modalities may prove to be viable options in future. The follow-up results of clinical studies will evaluate the long-term impact of DCBs.

Systems of local drug delivery to arterial wall for prevention of in-stent restenosis

New generation, drug-eluting stents used in the treatment of coronary and peripheral atherosclerotic disease (CPAD) significantly reduced restenosis and revascularization rates as well as frequency of thrombosis as compared to bare metal stents and first-generation drug eluting stents. However, despite fast development of this technology several reports have been published recently that describe cases of late and very late stent thrombosis, restenosis and neoatheroslerosis within arterial segments with previously implanted stents. For this reason many research are being conducted with the aim to design alternative methods for intra-arterial drugs delivery in order to reduce restenosis and revascularization rates, yet eliminating adverse effects mentioned above. One of possibilities is lipophilic and antiproliferative drug coated balloon technology, which offers high drug concentration in arterial tissue and restenotic effect in selected clinical situations despite the short balloon inflation time. A particularly interesting option is intra-arterial delivery of drugs with different mechanisms of action, regardless of their lipophilicity by loading them into biodegradable nanospheres. In this paper, currently used systems for local drug delivery have been described including their limitations and opportunities. In addition, we provided a brief description of the project sponsored by Polpharma Scientific Foundation, which aimed to evaluate potentials of local delivery of biodegradable nanospheres loaded with everolimus, which could be used to reduce restenosis rate after stent implantation.

New developments in the clinical use of drug-coated balloon catheters in peripheral arterial disease.

Peripheral arterial disease (PAD) involving the lower extremity is a major source of morbidity and mortality. Clinical manifestations of PAD span the spectrum from lifestyle limiting claudication to ulceration and gangrene leading to amputation. Advancements including balloon angioplasty, self-expanding stents, drug-eluting stents, and atherectomy have resulted in high technical success rates for endovascular therapy in patients with PAD. However, these advances have been limited by somewhat high rates of clinical restenosis and clinically driven target lesion revascularization. The recent introduction of drug-coated balloon technology shows promise in limiting neointimal hyperplasia induced by vascular injury after endovascular therapies. This review summarizes the contemporary clinical data in the emerging area of drug-coated balloons.

Drug-Coated Balloons for Revascularization of Infrapopliteal Arteries: A Meta-Analysis of Randomized Trials.

The aim of this study was to perform a meta-analysis of randomized trials investigating the outcomes of patients undergoing percutaneous revascularization with drug-coated balloons (DCBs) for atherosclerotic disease of theinfrapopliteal arteries. The role of DCBs as revascularization therapy for infrapopliteal arteries represents a matter of ongoing controversy. Scientific databases were searched for randomized trials of DCB therapy for atherosclerotic disease of the infrapopliteal arteries. The primary efficacy and safety outcomes were target lesion revascularization and amputation, respectively. Secondary outcomes were death, major adverse events, Rutherford class 5 or 6, and late lumen loss. A total of 641 patients enrolled in 5 trials received DCBs (n= 378) or control therapy (uncoated balloons or drug-eluting stents; n= 263). Median follow-up duration was 12 months. Patients treated with DCBs had risk for target lesion revascularization (risk ratio: 0.71; 95% confidence interval [CI]: 0.47 to 1.09; p= 0.12), amputation (risk ratio: 1.01; 95% CI: 0.65 to 1.58; p= 0.95), death (risk ratio: 1.14; 95% CI: 0.71 to 1.82; p= 0.59), major adverse events (risk ratio: 0.92; 95% CI: 0.59 to 1.43; p= 0.70), and Rutherford class 5 or 6 (risk ratio: 0.87; 95% CI: 0.46 to 1.62; p= 0.65) comparable with that of patients treated with control therapy. Lesions treated with DCBs showed lower late lumen loss(weighted mean difference-0.41; 95% CI:-0.79 to-0.03; p= 0.04) compared with those treated with controltherapy. In comparison with uncoated balloons or drug-eluting stents, the treatment of infrapopliteal arteries with DCBs is associated with similar clinical outcomes and favorable angiographic efficacy at 1-year follow-up. Further studies in larger numbers of patients are still needed to definitively address the role of DCB technology in this setting. (Drug-coated balloon for revascularization of tibialpedal arteries: a meta-analysis of randomized trials; CRD42015029283).

SICI-GISE position paper on drug-coated balloon use in the coronary district

Drug-coated balloons are a new tool for the treatment of patients with coronary artery disease. The main feature of this technology is a rapid and homogeneous transfer of an antiproliferative drug (paclitaxel) to the vessel wall just at the time of balloon inflation, when neointimal proliferation, in response to angioplasty, is the highest. Moreover, drug-coated balloons share adjunctive advantages over stents: the absence of permanent scaffold and polymer, the respect of the original coronary anatomy, and limited inflammatory stimuli, thereby allowing for short-term dual antiplatelet therapy. At present, a variety of devices are available in the market, with limited scientific data for the vast majority of them. Thus, the Italian Society of Interventional Cardiology (SICI-GISE) decided to coordinate the efforts of a group of renowned experts in this field, in order to produce a position paper on the correct use of drug-coated balloons in all settings of coronary artery disease, giving a class of indication to each one, based on clinical evidence. This position paper represents a quick reference for operators, investigators and manufacturers to promote the understanding and the correct use of the drug-coated balloon technology in everyday clinical practice.

Drug-coated balloons in the treatment of femoro- and infra-popliteal lesions

Despite initially encouraging technical success after femoropopliteal percutaneous transluminal angioplasty (PTA), postprocedural restenosis remains the major challenge. Antiproliferative drugs applied via drug-coated balloons (DCBs) or drug-eluting stents suppress neointimal hyperplasia, the main cause of restenosis. The present article summarizes results of DCB treatments of femoropopliteal and infrapopliteal lesions and points out open questions. Major advantage of the DCB technology is leaving no stent scaffold behind and an immediate release of high drug concentrations. The superiority of DCB versus PTA was shown in several randomized clinical trials. Moreover, calcified lesions seem to impair the efficacy of DCB. Although mechanical abrasions have shown favorable periprocedural results, short and long-term impact is still controversial. Combinations of preceding debulking methods (atherectomy) with DCBs have shown promising results.

The current status of drug-coated balloons in percutaneous coronary and peripheral interventions

Through continued innovation, percutaneous treatment of coronary and peripheral stenoses has evolved rapidly since balloon angioplasty was first introduced three decades ago. Significant advances were made with the introduction of bare metal stents and subsequently drug-eluting stents, which expanded the possibility of successful revascularisation in complicated lesions. Despite these advantages, efforts are still ongoing to improve patient outcomes further. In recent years, drug-coated balloons have emerged as an exciting technology developed to overcome the limitations faced by drug-eluting stents, such as stent thrombosis and dependency on prolonged dual antiplatelet therapy, and may prove efficacious in complex subsets such as small vessels and diffuse lesions where stent results are suboptimal. Several drug-coated balloons developed for coronary and peripheral applications were evaluated recently in preclinical and clinical studies with encouraging results. Drug-coated balloons have proven effective in treating in-stent restenosis; however, there is accumulating evidence on their utility in other clinical scenarios. We present a timely review of the mechanisms of action, key preclinical studies, emerging clinical indications, current clinical trial results, and future perspectives of this novel drug-coated balloon technology as it seeks to establish its role in percutaneous intervention.

Drug‐coated balloon treatment of coronary artery disease: A position paper of the Italian Society of Interventional Cardiology

Drug-coated balloons are a new tool for the treatment of patients with coronary artery disease. The main feature of this technology is a rapid and homogenous transfer of an antiproliferative drug (paclitaxel) to the vessel wall just at the time of balloon inflation, when neointimal proliferation, in response to angioplasty, is the highest. Moreover, drug-coated balloons share adjuntive advantages over stents: the absence of permanent scaffold and polymer, the respect of the original coronary anatomy, and limited inflammatory stimuli, thereby allowing for short-term dual antiplatelet therapy. To this day, a lot of devices are available in the market, with limited scientific data for the vast majority of them. Thus, the Italian scientific society of interventional cardiologists GISE decided to coordinate the efforts of a group of reknown experts on the field, in order to obtain a Position Paper on the correct use of drug-coated balloons in all the settings of coronary artery disease, giving a class of indication to each one, based on the clinical evidence. This Position Paper represents a quick reference for operators, investigators, and manufactures to promote the understanding and the correct use of the drug-coated balloon technology in everyday clinical practice.

Paclitaxel-iopromide coated balloon followed by “bail-out” bare metal stent in porcine iliofemoral arteries: first report on biological effects in peripheral circulation

Despite recent abundance of data on drug-coated balloon technology, the biological effects of paclitaxel coated balloon (PCB) treatment followed by bare metal stent (BMS) implantation in peripheral arteries (simulating bail-out stenting, a common clinical scenario), have not been published. PCB technology containing a paclitaxel-iopromide coating and identical iopromide-coated controls (without paclitaxel) were used in 16 porcine ilio-femoral arteries. The biological effects of inflating one (PCBx1) or two sequential (PCBx2) paclitaxel coated balloons before BMS implantation were compared to the single application of a control balloon (CCBx1; contrast coated balloons). At 30 days PCBx2 displayed significantly reduced late lumen loss by angiography (58% reduction vs. CCBx1; p=0.04) and neointimal area by histomorphometry (35% reduction vs. CCBx1 and 30% vs. PCBx1; p=0.02). Similarly, percent area stenosis in the PCBx2 group was reduced by 45% as compared to CCBx1 and PCBx1 (p=0.04). At this time, all parameters of vessel wall healing (including injury score, inflammation, and endothelialisation) following drug coated balloon treatment were comparable to the control group. Paclitaxel delivery to porcine ilio-femorals using PCB followed by BMS implantation effectively decreased neointimal proliferation. More extensive and prolonged proliferative response of the vessel after stenting (necessitating higher drug dose) could potentially explain the undetectable effect of PEBx1 relative to CCBx1 in this pilot study. Histological analysis confirmed the safety and biocompatibility of PCB technology.

Drug-Coated Balloons for the Prevention of Vascular Restenosis

From early in the history of percutaneous cardiovascular intervention, restenosis has been one of the most important clinical and biological measures of success, and a great deal of effort has been put into understanding the mechanisms responsible.1,2 Restenosis is the result of the interaction of a variety of mechanical and biological processes that begin immediately after balloon injury, including early vessel recoil,3,4 negative vascular remodeling,5 and excessive neointimal proliferation.5–7 The most important limitations of balloon angioplasty, abrupt vessel closure resulting from elastic recoil and occlusive plaque dissection, were effectively solved by the introduction of balloon-expandable stents.8 However, in-stent restenosis (ISR), the result of the initial injury and the vascular response to the implanted metallic prosthesis leading to excessive neointimal proliferation, remained as the most important cause of failure of these devices.9,10 Drug-eluting stents (DES) effectively reduced ISR by addressing the biological mechanisms of neointimal proliferation and have become the mainstay of the interventional treatment of coronary atherosclerotic disease.11 However, the demonstrated efficacy of DES is balanced by the small but unpredictable risk of very late stent thrombosis thought to be due to delayed vascular healing resulting from either the initial antiproliferative effect (and associated late acquired incomplete stent apposition) or a hypersensitivity reaction to the drug, polymer coating, or their combination.12,13 Moreover, beyond the coronary vasculature, there has been a paucity of effective therapies to manage restenosis after intervention. In recent years, drug-coated balloons (DCBs) have emerged as a therapeutic alternative in the interventional field.14 With this technology, short-term transfer of antiproliferative drugs to the arterial wall is achieved without the requirement of an implanted drug delivery system, thus potentially reducing the untoward effects associated with polymer-based stent technologies. In small clinical randomized trials, paclitaxel-coated balloons have been shown to be …