Drug-Coated Balloons: Applications in Interventional Cardiology

This book provides a comprehensive, up-to-date summary of drug-coated balloon (DCB) technology and the role of DCBs in the treatment of coronary and peripheral arterial disease. In addition to clear explanation of how DCBs works, readers will find an enlightening analysis of the mistakes and successes of the past decade and the emergence of the latest delivery systems, which combine a more deliverable device with much improved drug delivery to the vessel wall. The full range of current applications of DCBs are reviewed in detail, drawing on the latest scientific evidence. Due attention is paid to newer devices, with provision of technical insights and documentation of the available clinical data. Ongoing research projects, remaining technical challenges, likely future directions, and reimbursement issues are also carefully considered. This book will be a useful tool for any interventional cardiologist, interventional radiologist, or vascular surgeon who wishes to acquire a deep knowledge of this technology and its application in both coronary and peripheral interventions.

• Language: English
• Publisher: Springer
• Release date: Jun 19, 2019
• ISBN: 9783319926001

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© Springer Nature Switzerland AG 2019

Bernardo Cortese (ed.)Drug-Coated Balloons https://doi.org/10.1007/978-3-319-92600-1_1

1. From Drug-Eluting Balloon to Drug-Coated Balloon … to Eradication of Intracoronary Metal, a New Ending Story

Patrick W. Serruys¹   and Kuniaki Takahashi²

(1)

Imperial College London, London, UK

(2)

Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Patrick W. Serruys

In October 1993, the team of the Thorax Center in Rotterdam transmitted three live cases to TCT in a 90-min session: the first one was a three-vessel disease treatment with three Palmaz-Schatz stents (not yet approved in the USA by the FDA) [1]; the second one was a recanalization of a CTO with a laser wire in a patient included in the TOTAL trial [2]; the third one was a drug-eluting balloon treatment (the Dispatch balloon) post balloon angioplasty [3].

Indeed, drug-eluting balloons have existed before drug-coated balloons. The first local drug delivery device for coronary application was the porous balloon, consisting of an angioplasty balloon with laser-made perforations around its circumference. This catheter, however, caused jet-stream lesions to the vessel wall because of the high local infusion pressure. Other infusion methods and a variety of infusion catheters were designed to overcome this limitation, such as controlled low-pressure infusion, microporous balloon, dual balloon, multi-channel balloon, drug delivery sleeve, or iontophoretic balloon. However, all devices had the drawback of not allowing simultaneous distal arterial perfusion. The duration of infusion and the amount of drug administered were thereby limited. The potential hazards of local arterial damage and absence of coronary perfusion while the drug is being delivered confined the use of these devices to the animal experimental laboratory. A quarter of century ago (in 1995), a new local drug infusion catheter (Dispatch Soimed Systems Inc.) was designed to overcome these aforementioned limitations by combining infusion and perfusion characteristics.

At that time, we used to administer 99mTc-labeled heparin through the drug-eluting balloon and during the live case (for the TCT) and as routine we used to push a gamma camera into the cath lab to visualize online, on the screen of the gamma camera, the increasing local radioactivity at the site of the balloon angioplasty [4] (see Figs. 1.1 and 1.2).

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Fig. 1.1

Distal part of the local drug delivery catheter (Dispatch) showing the deployed 20-mm-long nondilatational coil balloon. The coil consists of six balloon loops wrapped in a nonporous polyurethane sheath. When the loops are inflated, a central conduit for blood perfusion was deployed, and five external blood-free compartments were created. Drug solution entered these compartments through isolated slits in the catheter shaft located between the inflated coils

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Fig. 1.2

Offline image reconstruction at four different periods during the acquisition: (1) last 15 min of infusion; (2) 15 min, (3) 3 h, and (4) 6 h after infusion and coil-balloon removal. A single image represents 15 min of acquisition

Yes, indeed, more than 10 years before the use of drug-coated balloon we had a wave of research and hype with drug-coated balloons.

Heparin was known as a powerful inhibitor of smooth muscle cells—in vitro, and for sure we were impacting the vessel wall with the drug, as demonstrated by the remnant radioactivity for 24 h (Fig. 1.2).

Unfortunately, despite the scientifically documented administration of the drug into the vessel wall, it did not affect the neointimal hyperplasia.

I lost my interest in drug-eluting balloon and in 1997 Elisabeth Nabel from NHI tried to convince me that upregulation of P27 by a drug called Rapamycin would eliminate the exuberant neo-intimal hyperplasia induced by the baro-trauma of balloon angioplasty.

In 1999, Robert Falotico drew my attention to the neo-intimal inhibition obtained from a pig model treated with a stent-eluting Rapamycin. The rest is history—with Eduardo de Sousa we ushered into the era of drug-eluting stents. There were two drugs: one cytostatic Sirolimus and one cytotoxic Paclitaxel. My preference went to Sirolimus although I tested Paclitaxel in TAXUS II and III trials [5–8]. What was not my astonishment when in 2006 I was asked to review for the NEJM a paper on prevention of neo-intimal hyperplasia in patients with in-stent restenosis treated by Paclitaxel drug-coated balloon. I could not detect any methodologic flaws in the paper and I accepted the paper of Bruno Scheller in the NEJM [9].

It was in itself the start of a new era, exploring drug-coated balloon versus BMS or DES in restenosis, in primary lesion, in large vessel, in small vessel, in bifurcation, and so on. Fortunately, drug-coated balloon does not have to face the specter of late or very late thrombosis. Paclitaxel was initially used because of its lipophilicity. In the early days of drug-eluting stent era, we used to say that it sticks to the metal as benzene does.

A recent meta-analysis on the use of paclitaxel in the peripheral circulation has surprised some clinicians [10]. And, the saga about the correct report of the data is worrisome, but I have to remind the clinicians that animals, such as horses, chewing leaves of a Taxus hedge, may die—it is a powerful drug. But, as beautifully described in the monography of Bernardo Cortese, the technology has evolved. Limus are now used; biolimus A9, because of its lipophilic nature, could have a certain edge on the hydrophilic sirolimus. However, sirolimus encapsulated in lipidic microsphere would do the trick [11] (Figs. 1.3, 1.4, and 1.5) although nano-technology is luring around the corner to make its entry into the field. It seems like yesterday, but it was in 2013 that Pedro Lemos, Renu Virmani, and myself reported the preclinical work on that methodological approach. Figures 1.3, 1.4, and 1.5 describe the salient features of this technology, now widely applied in the clinical arena.

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Fig. 1.3

Schematic illustration of the ultrastructure of the nanoparticle containing sirolimus (nucleus, in green), incorporating the combination of two excipient carriers to allow penetration and release of the active agent. Excipient 1 is a lipid-based component with a hydrophilic head and two lipophilic tails, which is the basic unit of a bilayer membrane that encapsulates the particle (note the detail in the right upper panel). Excipient 2 is integrated in the particle envelope, comprising ~5% of the coating mass. It is a calcium-phosphorus-based component with enhanced hemocompatibility that is readily absorbed into the vessel wall and releases the encapsulated drug on variation in pH

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Fig. 1.4

(a) Scanning electron micrography of the nanocarrier drug-eluting stent formulation. From left to right: pre-crimped coated stent; balloon after removal of stent. (b) Scanning electron micrography of the nanocarrier drug-eluting balloon formulation (left panel). Right panel: high magnification microphotography of the nanocarrier coating

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Fig. 1.5

Temporal penetration of DTF-labeled sirolimus nanoparticles after drug-eluting balloon inflation, as assessed by confocal microscopy. The left panels show a diagrammatic representation and the mid- and right panels the actual cross-sectional images. At 1 h (upper panels), 60–70% of circumferential area was marked with DTF signal. No particle was seen below the internal elastic lamina. At 3 days (mid-panels), 30–40% of circumferential area presented DTF signal. The majority of particles were below the internal elastic lamina (some positive signals deeper in media). At 7 days (lower panels), 30–40% of circumferential area had DTF signal. Particles primarily in deep media, with rare extension into adventitia. A: adventitia; EEL: external elastic lamina; IEL: internal elastic lamina; L: lumen; M: media

The precise tailor-made use of the principle of drug-coated balloon is also described in detail in the monography. Nowadays, OCT imaging can provide precise dimensions of the vessel and guarantee correct fitting between the balloon dimension and the vessel size (Fig. 1.6).

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Fig. 1.6

QCA (quantitative coronary angiography) underestimates the real dimension (laminal flow of contrast medium in contact with the vessel wall is assessed by brightness profile; 2.8 mm, see figure). QIVUS (quantitative intravascular ultrasound) imaging overestimates the real dimension (ultrasound wave has to penetrate the vessel wall over 200 μm before being reflected; 3.2 mm, see figure). OCT (optical coherence tomography) measures the real dimension (light wave has to penetrate the vessel wall only over 20 μm before being reflected; 3.0 mm, see figure)

At some point, at least for stable angina the percutaneous treatment, even without implantation, will be challenged by powerful systemic pharmacological agents, such as monoclonal antibody against PCSK9, aiming at regression of coronary artery disease. Today, a reduction of 22% in revascularization rate has already been documented in the FOURIER trial [12]. Soon we will have to re-think our strategy of treatment and synergy of local and systemic treatment without permanent caging of the vessel with metal—a new Holy Grail!

Since the first stent implantation in 1969 by Dotter [13, 14], it took us more than 50 years to learn how to properly cage a coronary vessel [15]. It may take us as long to abandon the metallic cage as the method of treatment. This is one of the perspectives sketched in this remarkable monography by Bernardo Cortese.

References

1.

Serruys PW, de Jaegere P, Kiemeneij F, Macaya C, Rutsch W, Heyndrickx G, Emanuelsson H, Marco J, Legrand V, Materne P, et al. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. Benestent Study Group. N Engl J Med. 1994;331(8):489–95.Crossref

2.

Serruys PW, Hamburger JN, Koolen JJ, Fajadet J, Haude M, Klues H, Seabra-Gomes R, Corcos T, Hamm C, Pizzuli L, Meier B, Mathey D, Fleck E, Taeymans Y, Melkert R, Teunissen Y, Simon R. Total occlusion trial with angioplasty by using laser guidewire. The TOTAL trial. Eur Heart J. 2000;21(21):1797–805.Crossref

3.

Camenzind E, Kint PP, Di Mario C, Ligthart J, van der Giessen W, Boersma E, Serruys PW. Intracoronary heparin delivery in humans. Acute feasibility and long-term results. Circulation. 1995;92(9):2463–72.Crossref

4.

Camenzind E, Bakker WH, Reijs A, van Geijlswijk IM, Boersma E, Kutryk MJ, Krenning EP, Roelandt JR, Serruys PW. Site-specific intracoronary heparin delivery in humans after balloon angioplasty. A radioisotopic assessment of regional pharmacokinetics. Circulation. 1997;96(1):154–65.Crossref

5.

Tanabe K, Serruys PW, Degertekin M, Guagliumi G, Grube E, Chan C, Munzel T, Belardi J, Ruzyllo W, Bilodeau L, Kelbaek H, Ormiston J, Dawkins K, Roy L, Strauss BH, Disco C, Koglin J, Russell ME, Colombo A, TAXUS II Study Group. Chronic arterial responses to polymer-controlled paclitaxel-eluting stents: comparison with bare metal stents by serial intravascular ultrasound analyses: data from the randomized TAXUS-II trial. Circulation. 2004;109(2):196–200.Crossref

6.

Serruys PW, Degertekin M, Tanabe K, Russell ME, Guagliumi G, Webb J, Hamburger J, Rutsch W, Kaiser C, Whitbourn R, Camenzind E, Meredith I, Reeves F, Nienaber C, Benit E, Disco C, Koglin J, Colombo A, TAXUS II Study Group. Vascular responses at proximal and distal edges of paclitaxel-eluting stents: serial intravascular ultrasound analysis from the TAXUS II trial. Circulation. 2004;109(5):627–33.Crossref

7.

Tanabe K, Serruys PW, Degertekin M, Grube E, Guagliumi G, Urbaszek W, Bonnier J, Lablanche JM, Siminiak T, Nordrehaug J, Figulla H, Drzewiecki J, Banning A, Hauptmann K, Dudek D, Bruining N, Hamers R, Hoye A, Ligthart JM, Disco C, Koglin J, Russell ME, Colombo A, TAXUS II Study Group. Incomplete stent apposition after implantation of paclitaxel-eluting stents or bare metal stents: insights from the randomized TAXUS II trial. Circulation. 2005;111(7):900–5.Crossref

8.

Tanabe K, Serruys PW, Grube E, Smits PC, Selbach G, van der Giessen WJ, Staberock M, de Feyter P, Muller R, Regar E, Degertekin M, Ligthart JM, Disco C, Backx B, Russell ME. TAXUS III trial: in-stent restenosis treated with stent-based delivery of paclitaxel incorporated in a slow-release polymer formulation. Circulation. 2003;107(4):559–64.Crossref

9.

Scheller B, Hehrlein C, Bocksch W, Rutsch W, Haghi D, Dietz U, Bohm M, Speck U. Treatment of coronary in-stent restenosis with a paclitaxel-coated balloon catheter. N Engl J Med. 2006;355(20):2113–24.Crossref

10.

Katsanos K, Spiliopoulos S, Kitrou P, Krokidis M, Karnabatidis D. Risk of death following application of paclitaxel-coated balloons and stents in the femoropopliteal artery of the leg: a systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc. 2018;7(24):e011245.Crossref

11.

Lemos PA, Farooq V, Takimura CK, Gutierrez PS, Virmani R, Kolodgie F, Christians U, Kharlamov A, Doshi M, Sojitra P, van Beusekom HM, Serruys PW. Emerging technologies: polymer-free phospholipid encapsulated sirolimus nanocarriers for the controlled release of drug from a stent-plus-balloon or a stand-alone balloon catheter. EuroIntervention. 2013;9(1):148–56.Crossref

12.

Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, Kuder JF, Wang H, Liu T, Wasserman SM, Sever PS, Pedersen TR. FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713–22.Crossref

13.

Dotter CT, Buschmann RW, McKinney MK, Rosch J. Transluminal expandable nitinol coil stent grafting: preliminary report. Radiology. 1983;147(1):259–60.Crossref

14.

Dotter CT. Transluminally-placed coilspring endarterial tube grafts. Long-term patency in canine popliteal artery. Invest Radiol. 1969;4(5):329–32.Crossref

15.

Serruys PW, Garcia-Garcia HM, Onuma Y. From metallic cages to transient bioresorbable scaffolds: change in paradigm of coronary revascularization in the upcoming decade? Eur Heart J. 2012;33(1):16–25b.Crossref

© Springer Nature Switzerland AG 2019

Bernardo Cortese (ed.)Drug-Coated Balloons https://doi.org/10.1007/978-3-319-92600-1_2

2. History of Drug-Coated Balloons

Dario Buccheri¹ and Bernardo Cortese²  

(1)

Interventional Cardiology, Trapani Hospital, Trapani, Italy

(2)

Cardiac Department, San Carlo Clinic, Milano, Italy

Bernardo Cortese

The advent of balloon angioplasty (BA) for the treatment of coronary artery disease was performed by Andreas Grüntzig in 1977 [1] (Fig. 2.1) and represented a breakthrough in the field of cardiology: by that time, we can say that modern interventional cardiology was born.

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Fig. 2.1

Grüntzig in front of the poster that described experimental percutaneous dilatation of coronary artery stenosis, 49th Scientific Sessions of the American Heart Association, Miami Beach, Florida, November, 1975 (Photo by John Abele, with permission)

Subsequently, in 1986 the first bare-metal stent (BMS) was introduced as a bailout strategy in case of some frequently encountered complications: coronary artery dissection, recoil, or acute occlusion after BA. In few years, since the late 1980s, BMS implantation becomes routine during percutaneous interventions.

Unfortunately, BMSs were afflicted by a high restenosis rate quantifiable in about 20–40% of the cases [2]; thereafter in the early years of the new millennium, drug-eluting stent (DES) was introduced, with the aim of reducing the risk of in-stent restenosis (ISR). In fact, these devices have reduced greatly its incidence up to 10% of PCIs [2]. Over the years the DES has been strongly improved with newer antiproliferative drug and thinner strut thickness. However, ISR remains a problem, affecting about 5% of all PCIs [2, 3].

In this scenario, the drug-coated balloon (DCB) finds its initial rationale. In fact, these devices gained a Class I, level of evidence A in the latest European Society of Cardiology (ESC) guidelines, equal to DES for ISR treatment [4].

The initial idea was born on the fact that an antiproliferative drug, identified in paclitaxel (taxol) due to its high lipophilicity and characteristics, has shown microtubules assembly inhibition, thus contrasting the migration and proliferation of human arterial smooth muscle cells in vitro and the neointima formation in an in vivo experimental rabbit model [5].

In this scenario, Bruno Scheller and Ulrich Speck were attracted by this new idea in which paclitaxel showed a good result in the treatment and prevention of ISR, avoiding a further metal layer in the view of the fact that this intriguing strategy was not stent based to deliver an antiproliferative drug locally. In this light, Scheller et al. published, in 2002, their first study in which an antiproliferative drug, in this case the protaxel, was added to contrast media, namely, iopromide that served as a carrier for intravascular drug delivery, during coronary angiography in a porcine model [6]. The paclitaxel was successfully used as intracoronary antiproliferative drug preventing the restenosis. In this view, the pioneering study by Sheller et al. showed that taxane intracoronary application dissolved in a contrast medium is safe and efficient as an inhibitor of in-stent restenosis, not the same when the drug is administered intravenously [6]. The result was a relevant reduction in neointimal proliferation in previously implanted stents and an effective prevention after stent implantation [6].

Subsequently, the intriguing idea was to carry locally the drug for a single lesion treatment instead of one single vessel injection. In this view, the first results published by Scheller et al. arrived in 2004 when paclitaxel was shown an effective treatment in reducing neointimal proliferation in a porcine coronary model [7] as shown in Fig. 2.2, adapted from the original study.

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Fig. 2.2

In the study by Scheller et al. [7], a conventional balloon catheter was coated with paclitaxel by two different procedures: (1) EEE used ethyl acetate as the solvent and resulted in ≈2 μg paclitaxel per square millimeter of balloon surface, and (2) procedure Ac used acetone as the solvent and was completed with two concentrations of paclitaxel: a low dose (AcL), resulting in 1.3 μg/mm², and a regular dose (AcR), resulting in 2.5 μg/mm². This figure shows histological findings of the study in control group (a), EEER coating (b), AcL coating (c), and AcR coating (d). From Bruno Scheller et al. Circulation. 2004;110:810-814 (permission requested)

Despite initial skepticism about the efficacy of a single dose of antiproliferative drug to prevent restenosis, at the end of 2003, the first patient of the pivotal randomized study Paccocath ISR for BMS restenosis was enrolled [8]. Six-month angiographic follow-up showed mean (±SD) in-segment late luminal loss was 0.74 ± 0.86 mm in the uncoated-balloon group (UB) vs. 0.03 ± 0.48 mm in the paclitaxel-coated balloon group (PCB) (P = 0.002). A total of 10 of 23 patients (43%) in the UB had restenosis, as compared with 1 of 22 patients (5%) in the PCB (P = 0.002). At 12 months, the MACE rate was 31% in the UB and 4% in the PCB (P = 0.01) primarily driven by target lesion revascularization in six patients in the UB (P = 0.02) [8].

Following these initial good experiences, several in vitro and in vivo experiments investigating the coating methodology, drug adherence, and release started. The first specific matrix coated was the Paccocath, a mix consisting of paclitaxel and iopromide hydrophilic X-ray contrast medium (Ultravist) [7–10]. Particularly, Paccocath balloons were standard balloons angioplasty coated with a dose of 3 μg/mm² of paclitaxel in which iopromide had the role of assisting paclitaxel in vessel adherence and subsequent penetration, limiting the risk of drug distal embolization [7–10].

The idea to use an antiproliferative drug as taxane reducing neointima hyperplasia was extended to peripheral artery disease [11]. In parallel in 2008, the same DCB application was investigated for the treatment of superficial femoral artery disease with the publication of Local Taxane with Short Exposure for Reduction of Restenosis in Distal Arteries (THUNDER) trial by Tepe et al. [12]. In the latest study, 154 patients with femoropopliteal artery stenosis or occlusion were treated with standard balloon catheters coated with paclitaxel, uncoated balloons with paclitaxel dissolved in the contrast medium, or uncoated balloons without paclitaxel (control group). Six-month angiographic follow-up showed that mean late lumen loss (namely, the primary endpoint) was 1.7 ± 1.8 mm in the control group, as compared with 0.4 ± 1.2 mm (P < 0.001) in the group treated with paclitaxel-coated balloons and 2.2 ± 1.6 mm (P = 0.11) in the group treated with paclitaxel in the contrast medium. Furthermore, no adverse events were attributable to the paclitaxel-coated balloons. The rate of revascularization of target lesions at 6 months was 20 of 54 (37%) in the control group, 2 of 48 (4%) in the group treated with paclitaxel-coated balloons (P < 0.001 vs. control), and 15 of 52 (29%) in the group treated with paclitaxel in the contrast medium (P = 0.41 vs. control); at 24 months, the rates increased to 28 of 54 (52%), 7 of 48 (15%), and 21 of 52 (40%), respectively.

The perception on DCB safety and efficacy was implemented over the years and slowly supported by several spontaneous and sponsored studies, aiming to understand if and how DCB worked with the following background: (1) homogeneous release of an antiproliferative drug without a further permanent metal prosthesis; (2) immediate release without a durable polymer that could induce chronic inflammation, thus causing late and very late thrombosis; and (3) a concrete reduction in the duration of dual antiplatelet therapy.

The advantage of antiproliferative drug delivery directly to the vessel wall without the implantation of a metal prosthesis seemed an attractive solution for lower extremity peripheral artery disease in which mechanical stressors could cause stent fracture. Thus, in 2014 the FDA approved the use of DCB in the femoropopliteal arterial bed.

Although first-generation DCB employed paclitaxel as an antiproliferative drug, it should be stressed that a class effect does not exist for these devices, mostly due to the different carriers used.

References

1.

Gruntzig A. Transluminal dilatation of coronary-artery stenosis. Lancet. 1978;311:263.Crossref

2.

Byrne RA, Joner M, Kastrati A. Stent thrombosis and restenosis: what have we learned and where are we going? The Andreas Grüntzig Lecture ESC 2014. Eur Heart J. 2015;36:3320–31.Crossref

3.

Buccheri D, Piraino D, Andolina G, Cortese B. Understanding and managing in-stent restenosis: a review of clinical data, from pathogenesis to treatment. J Thorac Dis. 2016;8:E1150–62.Crossref

4.

Authors/Task Force members, Windecker S, Kolh P, et al. 2014 ESC/EACTS guidelines on myocardial revascularization: the task force on myocardial revascularization of the European association for cardio-thoracic surgery (EACTS) developed with the special contribution of the European association of percutaneous cardiovascular interventions (EAPCI). Eur Heart J. 2014;35:2541–619.Crossref

5.

Axel DI, Kunert W, Göggelmann C, Oberhoff M, Herdeg C, Küttner A, Wild DH, Brehm BR, Riessen R, Köveker G, Karsch KR. Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery. Circulation. 1997;96:636–45.Crossref

6.

Scheller B, Speck U, Schmitt A, et al. Addition of paclitaxel to contrast media prevents restenosis after coronary stent implantation. J Am Coll Cardiol. 2003;42:1415–20.Crossref

7.

Scheller B, Speck U, Abramjuk C, et al. Paclitaxel balloon coating – a novel method for prevention and therapy of restenosis. Circulation. 2004;110:810–4.Crossref

8.

Scheller B, Hehrlein C, Bocksch W, et al. Treatment of in-stent restenosis with a paclitaxel coated balloon catheter. N Engl J Med. 2006;355:2113–24.Crossref

9.

Speck U, Scheller B, Abramjuk C, et al. Neointima inhibition: comparison of effectiveness of non-stent-based local drug delivery and a drug eluting stent in porcine coronary arteries. Radiology. 2006;240:411–18.17.Crossref

10.

Scheller B, Speck U, Romeike B, et al. Contrast media as a carrier for local drug delivery: successful inhibition of neointimal proliferation in the porcine coronary stent model. Eur Heart J. 2003;24:1462–7.Crossref

11.

Albrecht T, Speck U, Baier C, et al. Reduction of stenosis due to intimal hyperplasia after stent supported angioplasty of peripheral arteries by local administration of paclitaxel in swine. Invest Radiol. 2007;42:579–8.Crossref

12.

Tepe G, Zeller T, Albrecht T, et al. Local delivery of paclitaxel to inhibit restenosis during angioplasty of the leg. N Engl J Med. 2008;358:689–99.Crossref

© Springer Nature Switzerland AG 2019

Bernardo Cortese (ed.)Drug-Coated Balloons https://doi.org/10.1007/978-3-319-92600-1_3

3. Previous Mistakes with DCB Technology, and How to Prevent Them in the Future

Dario Buccheri¹ and Bernardo Cortese²  

(1)

Interventional Cardiology, Trapani Hospital, Trapani, Italy

(2)

Cardiac Department, San Carlo Clinic, Milano, Italy

Bernardo Cortese

Drug-coated balloon (DCB) is a relatively novel device for coronary and peripheral artery disease management [1]. It consists in a conventional balloon angioplasty covered by an antiproliferative drug. This technology allows to bring high concentration of an antiproliferative drug with rapid local delivery without the implantation of an external prosthesis like a metal stent or a scaffold, technologies associated with some late-occurring thrombotic events. In this light, the shorter dual antiplatelet therapy (DAPT) duration usually required with DCB may be an advantage because it warrants a reduced bleeding risk, especially in high-risk and compromised patients.

Although in the past few years stent technology has greatly improved the treatment of coronary artery disease patients, there are some limitations including stent performance in small vessel disease, the need for longer DAPT duration, treatment of in-stent restenosis, and a persistent although low risk of late/very late thrombosis. Moreover, a newer metal layer on a previously implanted stent as in the case of in-stent restenosis could cause a not negligible compromise in vasomotricity and damage the ostia of collaterals vessels [2]. In this view, the idea that a device allows the treatment of coronary artery lesions with an antiproliferative drug without a permanent prosthesis seems really intriguing.

However, especially the first DCB technologies shared some important limitations that concurred to further improvements into newer, more performing devices.