The publication of the first-in-human data on the treatment of in-stent restenosis in the 2000s was the starting point for drug-coated balloon (DCB) therapy in coronary artery disease1. The next logical step was to investigate DCB in de novo lesions. At that time, the lessons learned from the pioneers of coronary angioplasty had largely been eclipsed2, and direct stent implantation was preferred. It was also believed that de novo lesions required stent implantation. The role of DCB could be an adjunct to stents, creating a “polymer-free” drug-eluting stent (DES). However, in the PEPCAD I study3, we treated a series of patients with lesions in small coronary arteries. For this trial, the only DCB balloon diameter available was 2.5 mm, lesion preparation was an unknown term, and there were no clear rules on how to deal with dissections. Surprisingly, 70% of patients were suitable for a DCB-only strategy. Those patients showed favourable angiographic and clinical outcomes. In contrast, patients who underwent additional bare metal stent (BMS) implantation had an excess in restenosis and reinterventions, especially in case of geographical mismatch between the DCB and the stent3.
These findings strongly discouraged the combination of DCB and BMS, which could ultimately have meant the end of the de novo concept for DCB. On the other hand, the results for a “DCB-only” approach were surprisingly favourable, raising the question of whether it was possible to distinguish between lesions that could be treated with DCB alone and those that would require stent implantation. In May 2010, we organised the first meeting of the, initially German, later international, DCB Consensus Group. We proposed the concept of predilatation to identify lesions in which balloon dilatation caused dissection. In October 2010, the first Berlin DCB meeting, titled “Balloon angioplasty reborn”, was held with more than 400 attendees. The proceedings were published in a special edition of EuroIntervention4 (Figure 1). These events formed the basis for the DCB Consensus Group recommendations56, the Academic Research Consortium (ARC) DCB Consensus78, and became the starting point for the newly founded DCB Club29.
Fezzi and colleagues deserve recognition and congratulations for their contribution to the growing clinical evidence of DCB therapy10. In this issue of AsiaIntervention, they present the results of the PICCOLETO VI study − comparing the angiographic and physiological outcomes of various DCB technologies in treating de novo coronary artery disease, including follow-up angiography at 5-9 months10.
A total of 227 lesions treated either with paclitaxel-coated balloons (PCB; 6 different brands; n=148) or sirolimus-coated balloons (SCB; 3 different brands; n=79) were included. Quantitative coronary angiography (QCA) parameters and Murray law-based quantitative flow ratio (μFR) were measured and calculated. PCB showed lower late lumen loss and a higher prevalence of late lumen gain, which is in line with other mechanistic randomised angiographic endpoint studies111213. Furthermore, the frequency of a μFR ≤0.80 at follow-up angiography was almost twice as high in lesions treated with SCB. However, this difference was not reflected in different clinical outcomes. A post-DCB μFR ≤0.86 was a predictor of follow-up ischaemia, whereas no significant interaction was observed for a post-DCB angiographic degree of stenosis ≥30%. Their results are noteworthy and may serve as a starting point for prospective randomised trials focusing on physiology-based primary endpoints. However, they should be viewed with caution due to the retrospective design and the mix of different DCB, lacking a class effect in both PCB and SCB.
Angiography is still the workhorse for DCB application. The criteria for successful lesion preparation as a prerequisite for a “DCB-only” strategy are angiographic56 and are used in large-scale clinical trials. However, it should be noted that these criteria are based purely on expert opinions. For example, the question arises as to whether the target of 30% diameter stenosis is appropriate. In the treatment of in-stent restenosis, the achievement of a less than 20% diameter stenosis, as measured by QCA, has been shown to be predictive of a low target lesion revascularisation rate14.
Dissections continue to be classified according to the old American Heart Association classification15. However, this classification originates from a time when dual platelet inhibition was not available and modern techniques, such as cutting or scoring balloons and calcium modification techniques, were not yet available. A simpler, DCB-oriented classification − discriminating between a “safe to leave” versus a “need to stent” dissection − may become more appropriate16. “Safe to leave” are dissections with visible dissections but Thrombolysis in Myocardial Infarction (TIMI) 3 flow and no persistent contrast staining. Up to 30% of stable luminal compromise, such as that seen with recoil, is considered safe. In contrast, dissections with reduced TIMI flow (due to the dissection rather than no-reflow), persistent or accumulating contrast, and/or evidence of progressive lumen compromise due to an accumulating intramural haematoma remain indications for stenting. This also includes spiral dissections16.
The roles of intravascular imaging (IVI)1718 and physiology19 in DCB therapy remain elusive. Stents create a defined static lumen that, if anything, can change over time due to the formation of restenosis. Data from large clinical studies are available for both IVI and physiology in this setting. The primary outcome achieved with angioplasty alone after DCB is subject to dynamic changes due to late lumen enlargement20 or vessel shrinkage and the return of vasomotion21. This also means that geometric and physiological parameters measured at rest may fluctuate during exercise. Understanding these relationships will probably be more challenging for DCB therapy than in the case of stent treatment.
Figure 1. First DCB Consensus Meetings and publications introducing the concept of ‘DCB-only’. A) Flyer for the first DCB Berlin meeting in October 2010; (B) cover of the EuroIntervention Supplement 2011; (C) flyer from the second DCB Berlin meeting in November 2012. DCB: drug-coated balloon
Conflict of interest statement
B. Scheller is a shareholder of InnoRa GmbH; and received lecture fees and advisory board honoraria from B.Braun, Medtronic, and Cordis. F. X. Kleber reports no conflicts of interest related to this editorial.