Expert Review of Cardiovascular Therapy

ISSN: 1477-9072 (Print) 1744-8344 (Online) Journal homepage: http://www.tandfonline.com/loi/ierk20

Drug-coated balloons in interventional cardiology Francesco Giannini, Charbel Naim, Charis Costopoulos, Azeem Latib & Antonio Colombo To cite this article: Francesco Giannini, Charbel Naim, Charis Costopoulos, Azeem Latib & Antonio Colombo (2013) Drug-coated balloons in interventional cardiology, Expert Review of Cardiovascular Therapy, 11:10, 1379-1391 To link to this article: http://dx.doi.org/10.1586/14779072.2013.837758

Published online: 10 Jan 2014.

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Date: 05 November 2015, At: 22:26

THEMED ARTICLE y Stents + Devices

Review

Drug-coated balloons in interventional cardiology Downloaded by [University of California Santa Barbara] at 22:26 05 November 2015

Expert Rev. Cardiovasc. Ther. 11(10), 1379–1391 (2013)

Francesco Giannini1, Charbel Naim1, Charis Costopoulos1–3, Azeem Latib*1,2 and Antonio Colombo1,2 1 Interventional Cardiology Unit, San Raffaele Scientific Institute, Milan, Italy 2 Interventional Cardiology Unit, EMO-GVM Centro Cuore Columbus, 48 Via M. Buonarroti, 20145 Milan, Italy 3 Imperial College London, London, UK *Author for correspondence: Tel.: +39 024 812 920 Fax: +39 024 8193 433 [email protected]

www.expert-reviews.com

Over the last few years, drug-coated balloon (DCB) therapy has emerged as a promising therapeutic intervention for the management of obstructive cardiovascular disease. The dictum of this novel technology is that effective prevention of restenosis can be achieved by the short-term transfer of antiproliferative drug to local arterial tissue by means of a single prolonged balloon angioplasty dilatation. Its main attraction is that no foreign body is implanted eliminating thus the risk of late inflammatory response to device components without preventing positive remodeling. Here, we discuss the evidence regarding the effectiveness of DCB in different lesion types and clinical settings as well as the types of DCB commercially available or under development. KEYWORDS: bailout stenting • bifurcation lesion • coronary artery disease • de novo coronary lesion • diffuse coronary disease • drug carrier • drug-coated balloon • excipient • in-stent restenosis • paclitaxel • percutaneous coronary intervention • semicompliant balloons • small vessel disease

Local drug release into the vessel wall is currently the dominant strategy for the prevention of restenosis [1]. Drug-eluting stents (DESs) have become the mainstay of current revascularization practice since they dramatically reduce the need for re-intervention as compared with bare metal stents (BMSs) [2]. The superiority of DES over BMS has been demonstrated in every lesion subset in which they have been evaluated [3], including de novo atherosclerotic disease of native and graft vessels [4] and in-stent restenosis (ISR) after BMS or DES implantation [5,6]. The paclitaxel drug-coated balloon (DCB) is an emerging device in percutaneous coronary intervention (PCI) that was developed to circumvent some of the limitations faced by DES. These limitations include late and very late stent thrombosis (ST) [7], risk of bleeding associated with prolonged dual antiplatelet therapy (DAPT) [8] and reduced efficacy in complex patient and lesion subsets [9]. DCBs are semicompliant angioplasty balloons covered with an antirestenotic drug that is rapidly released locally into the vessel wall during balloon contact. The two main DCB components are the vehicle for drug-elution (carriers/excipients) and the antiproliferative drug. Animal studies have demonstrated that antiproliferative drug delivery can be adequately achieved from the balloon surface into the vessel wall only with a matrix compound [10]. Similarly, Radke et al. compared

10.1586/14779072.2013.837758

various DCB using different drug-delivery formulations and confirmed that effective excipients are necessary to accomplish successful tissue transfer of the drug from a balloon surface [11]. Importantly, in vitro and in vivo models showed that during angioplasty with DCB, contact between vascular smooth muscle cells and paclitaxel, a highly lipophilic anti-neoplastic drug, is sufficient to provide long-lasting inhibition of cell proliferation [12–14]. As a result, paclitaxel became the sole drug utilized in most currently available DCB, with other drugs under investigation [15]. It remains to be seen whether refinement of methods of drug delivery from balloons will enable effective use of ‘limus’ drugs for DCB in the hope to repeat the success they have achieved as a component of DES, where evidence shows that drugs of this family are safer and more effective than paclitaxel [3]. All the above-mentioned aspects render the use of this device appealing and to date there have been a number of randomized studies that have evaluated DCB versus plain old balloon angioplasty (POBA), DES and BMS in different settings. DCB use in small vessel disease

Small coronary vessels remain a lesion subset in which DES are associated with relatively high restenosis rates [16,17]. The potential advantage of DCB in this setting is less vessel


2013 Informa UK Ltd

ISSN 1477-9072

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Review

Giannini, Naim, Costopoulos, Latib & Colombo

Downloaded by [University of California Santa Barbara] at 22:26 05 November 2015

Table 1. Clinical trials of drug-coated balloon use in small vessel disease. Ref.

Study

Design

Patients (n)

Primary end point (F-Up; months)

TLR, (%; F-Up; months)

Bailout stent rate (%)

PEPCAD I (single-center, single-arm study)

SeQuent please

118

LLL 0.18 mm in DCB only, 0.73 in DCB + BMS (6)

4.9 in DCB only, 27.1 in DCB + BMS (12)

28

[19]

PICCOLETTO (randomized, single-center study)

Dior I versus Taxus

57

Diameter stenosis 43.6% versus 24.3% (6) Noninferiority not met

32.1 versus 10.3 (9)

36

[20]

Spanish DIOR registry

Dior I/II

103

LLL 0.34 mm (6)

3 (12)

7

[21]

BELLO (randomized, multicenter trial)

In.Pact Falcon versus Taxus

182

LLL 0.09 versus 0.30 mm (6) Superiority of DCB

4.4 versus 7.7 (6)

20

[22]

BMS: Bare metal stents; DCB: Drug-coated balloon; F-Up: Follow-up; TLR: Target lesion revascularization.

wall inflammation in the absence of metallic stents and polymer, while allowing the artery’s original anatomy to remain intact, thus reducing abnormal flow patterns and permitting positive remodeling of the vessel [18]. TABLE 1 shows the studies that have evaluated the role of the DCB in the treatment of small coronary vessel disease. The first study to explore DCB use in small vessels was the Paclitaxel Eluting PTCA Balloon in Coronary Artery Disease (PEPCAD) I study, a single-arm trial investigating SeQuent Please DCB (B Braun Melsungen AG, Berlin, Germany) in vessels with a mean diameter of 2.36 mm [19]. The DCB-only group achieved impressive angiographic and clinical results at 6 months (binary restenosis: 5.5%; target lesion revascularization [TLR]: 4.9%). By contrast, 28% of patients who had BMS implanted after DCB fared much worse, with eight-times higher restenosis and five-times higher TLR. Most restenosis (77%) occurred at the stent edges, highlighting the potential pitfall of geographic mismatch where a longer BMS was placed outside the DCB-treated area. Vessel thrombosis occurred in 6.3% of the DCB + BMS group and in no patients who were treated only with DCB, despite a longer duration of DAPT in the former group (3 vs 1 month). The Paclitaxel-Coated Balloon Versus Drug-Eluting Stent During Percutaneous Coronary Intervention of Small Coronary Vessels (PICCOLETTO) study was the first randomized trial, comparing first-generation Dior-I DCB (Eurocor, Bonn, Germany) with Taxus Liberte` paclitaxel-eluting stent (PES, Boston Scientific Corporation, Natick, MA, USA), in vessels