By Robert Byrne
The development of drug-coated balloon angioplasty has represented a significant milestone in the evolution of percutaneous intervention both for obstructive coronary and peripheral arterial disease.
Although many clinicians and investigators were initially sceptical that a single application drug-coated balloon angioplasty could achieve a clinically relevant impact, preclinical studies along with initial randomised clinical trials have clearly demonstrated that non-stent based local drug delivery with drug-coated balloon catheters can impart effective local tissue drug concentrations and durable antirestenotic efficacy. Moreover drug-coated balloon angioplasty has a number of theoretical advantages over intervention with drug-eluting stent implantation. These include a broader area of surface contact than stents, more homogenous drug distribution, absence of stent footprint or polymer residue, and restoration of normal vessel anatomy/function.
Greatest success has been seen with coatings that combine lipophilic paclitaxel with a hydrophilic spacer or excipient (eg. iopromide, citrate) to maximise drug transfer and tissue retention in the limited time window afforded by a single balloon dilatation. With this technology, a relatively brief 30–60 balloon inflation results in effective local tissue concentrations and sustained inhibition of neointimal growth. Preclinical investigation has documented a largely favourable safety profile; importantly, however, evidence of increased arterial wall fibrin deposition is seen in comparison with plain balloon angioplasty and this seems to serve as a signature of effective drug transfer.
Due to the comparatively high benchmark of contemporary drug-eluting stents, clinical applications most suited to drug-coated balloon therapy are those where stent implantation is not desirable or less effective—eg. in-stent restenosis, lesions in small vessels, and bifurcation lesions. The most compelling clinical trial data comes from the setting of coronary in-stent restenosis. Randomised trials with drug-coated balloon for restenosis within bare metal (eg. PACCOCATH-ISR, PEPCAD-II, RIBS-V) as well as within drug-eluting stents (PEPCAD-DES, ISAR-DESIRE 3) have shown results comparable to those with repeat stenting with drug-eluting stents and superior to those with plain balloon angioplasty. Indeed by obviating the need for further stent implantation, drug-coated balloon angioplasty may be the treatment of choice. There remain, however, open questions regarding drug-coated balloon angioplasty for drug-eluting stent in-stent restenosis including long-term follow-up data as well as direct comparison trials with drug-coated balloons versus high performance current generation drug-eluting stents (though trials such as RIBS-IV are on-going). Moreover, there is also the issue whether lesion preparation with cutting balloon prior to drug-coated balloon therapy can further improve outcomes remains under investigation (eg. ISAR-DESIRE 4).
Against this, results with drug-coated balloon angioplasty for de novo coronary disease have been largely disappointing to date. The data might be considered in two categories. Firstly drug-coated balloon angioplasty combined with default bare metal stenting; in essence, this represents an alternative to standard drug-eluting stenting. The available data from trials such as PEPCAD-III has been negative and this approach seems to lack both clinical rationale and supportive data. A second category for drug-coated balloon angioplasty is as a “stand-alone therapy” with additional stent implantation only in bailout situations. Such a stent sparing strategy challenges the dogma of default stent implantation. Initial clinical trials have focused on intervention for lesions in small coronary vessels. The rationale for this is that stents fare poorly in these lesions, though arguably contemporary drug-eluting stents are particularly difficult to beat in this setting, due to the unique combination of high acute gain and low late loss. Indeed the published trials comparing a drug-coated balloon only strategy to standard stenting with drug-eluting have not been particularly encouraging (eg. PICCOLETO, BELLO). In addition, specific trials showing an advantage for drug-coated balloon use in bifurcation intervention have not been realised to date. It remains possible, however, that better performing balloon catheters may yet deliver improved outcomes with a drug-coated balloon only approach.
In summary, although drug-coated balloon therapy has been a significant innovation with relevance for everyday practice, convincing data in the coronary arena exists thus far only for the treatment of in-stent restenosis. Indeed, despite many years of clinical experience with drug-coated balloons, the number of high-quality, randomised clinical trials published in the peer-reviewed literature is low. Further data are needed across the spectrum of clinical indications. In particular, there is an urgent need for large-scale clinical trials with broad inclusion criteria, additional studies in de novo coronary disease and specific trials addressing the optimal duration of dual antiplatelet therapy in drug-coated balloon-treated patients.
Robert A Byrne, Deutsches Herzzentrum, Technische Universität, Munich, Germany.
Conflicts of interest: Robert Byrne has received speaker’s fees from B. Braun and Biotronik.