This advertorial is sponsored by B Braun Melsungen AG
Drug-coated balloons (DCBs) are building towards a new momentum in percutaneous coronary intervention (PCI) with increased interest in the potential advantages that these devices can offer over drug-eluting stents (DES) in a range of settings for the treatment of coronary artery disease (CAD). This growing understanding of the role of DCBs was brought into focus at DCB Days (8–9 October, Berlin, Germany), a two-day advanced training course hosted by B Braun at the prestigious Aesculap Academy in the German capital. The event saw experts in DCB-PCI from across the world sharing the latest data, insights and experience to underscore how DCBs—in particular the SeQuent DCB (B Braun) family of devices—have become an essential tool in the modern PCI toolkit.
“Leaving nothing behind” in the coronary vessels is not a new concept, attendees of the event heard—with roots back to the first-in-man coronary angioplasties performed in Zürich, Switzerland, by the godfather of interventional medicine Andreas Grüntzig. PCI practice has moved away from this idea in subsequent decades as the DES has become the dominant technology for interventional cardiologists to reopen coronary arteries. But, the “leave nothing behind” concept is experiencing a modern renaissance with the latest generation of cath lab operators waking up to the benefits that DCBs can bring to their practice, and more clinical evidence being gathered to support this approach in a wide range of clinical scenarios.
“I remember when this room was not packed out,” said DCB Days course director Raban Jeger (Triemli Hospital Zürich, Zürich, Switzerland) in his opening to a busy auditorium at the 2024 event, reflecting on how interest in this area of cardiology continues to gather pace. “This is important because DCBs have now become a real tool for the treatment of CAD. In the beginning it was really a technique that not many people adopted. Today, we have lots of believers.”
Jeger spoke alongside his fellow course directors, Fernando Alfonso (La Princesa University Hospital, Madrid, Spain) and Victor Jiménez (Hospital Álvaro Cunqueiro, Vigo, Spain), all three of whom are among Europe’s leading proponents of DCB therapy. The group worked together to craft a programme that encompassed the fundamentals of DCB angioplasty, touching on topics that range from the important role of lesion preparation, the use of imaging tools to optimise outcomes, emerging data on the expanding clinical indications for DCB usage, understanding the different properties of the available drug coatings and how these could confer benefits in different scenarios, and the fundamentals to establishing a DCB programme. Talks were punctuated by both live and recorded cases to demonstrate DCB-PCI in action and to illustrate key learning points. An engaged audience of around 150 attendees from more than 10 countries joined the course to understand how DCBs can play a greater role in their practice.
Attendees were taken “behind the scenes” at the drivers pushing forward the current global momentum for DCB-PCI, learning about the evolution of PCI and how technological developments over the years have been shaped by clinical need. Stents were first used to prevent early vessel closure caused by flow-limiting dissection, aiming to restore blood flow. Later, new techniques and tools were developed to improve lesion preparation, enhancing initial lumen gain to address residual stenosis and vascular recoil. Later, vessel thrombosis was addressed through advances in antithrombotic therapies and dual antiplatelet therapy (DAPT). DES then emerged as a solution to the challenge of overcoming restenosis due to neointimal proliferation or neoatherosclerosis. Additional technologies, including bioabsorbable scaffolds, have been geared towards vascular restoration, facilitating local drug delivery without the need for a permanent implant, and this has ultimately paved the way for DCBs as the next step for optimising PCI, providing a way of delivering anti-stenotic drugs to the vessel wall whilst leaving no permanent metallic structure behind.
Overcoming DES limitations
“The fact that stents have limitations in certain clinical and anatomic conditions led to the need to develop some other techniques,” said Jeger, detailing the 2020 international consensus statement from the International DCB Consensus Group, which sets out best practice for DCB-PCI. “These recommendations were based on the fact that, at the time, implants in CAD did have big problems. An event rate of more than 2% per year is quite cumbersome.”
The consensus document, which, despite being four years old, still remains relevant to present-day practice, according to Jeger, contains various sections that include technical considerations about the choice of DCB, lesion preparation, the role of functional measurements and intravascular imaging, delivery of the DCB, as well as the angiographic and clinical indications that are best suited for DCB-PCI, and future perspectives on DCBs.
“In the consensus group recommendations, we discussed a couple of indications; of course in-stent restenosis (ISR) has been examined in depth, this is a clear indication, then high bleeding risk, small vessels, bifurcations—these are the classical indications for DCBs,” said Jeger, commenting on some of the situations in which DCB-PCI has been considered to be an advantageous approach, and in which evidence and experience is growing. “We can’t say for all instances that this is the way to go, but in these indications, we have the best results. We think that in special situations where stents are not really working well, DCBs could be a good alternative.”
Indications: Established and emerging
Presentations offered a deep dive into the specific indications that may favour DCBs, focusing on ISR, bifurcation lesions, chronic total occlusion (CTO) and diffuse disease, examining present data and probing where further research is needed.
Alfonso argued in favour of DCBs as the gold standard for the treatment of ISR, commenting that in patients who have already been implanted with multiple layers of metal, further stent implantation is not an “elegant” solution to the problem.
Delegates learned that evidence to date has established DCBs as a first-line option for the treatment of ISR, with 2018 guidelines from the European Society of Cardiology (ESC) and the European Association of Cardio-Thoracic Surgery (EACTS) on myocardial revascularisation bestowing a class I recommendation—with the level of evidence A—for the use of DCBs in this setting. This recommendation is based largely on studies performed with the SeQuent paclitaxel and iopromide coating, including the PACCOATH ISR I and II and PEPCAD trials, with the guidelines noting “a class effect for all DCBs cannot be assumed”.
Alfonso also outlined some of the occasions where operators may choose to elect for DCB-PCI, citing cases where there is evidence of resistant under-expansion or optimal initial angiographic results. In the first instance of ISR, he commented, many operators may feel that using a DCB could be a suitable strategy, as they can return to use a DES if they are not satisfied with the result.
A perceived advantage of the DCB-PCI approach is that patients may only require a shorter duration of DAPT following their procedure, and Tuomas Rissanen (North Karelia Central Hospital, Joensuu, Finland) touched on how the use of DCBs can reduce the risk of bleeding in patients seen to be at high bleeding risk (HBR).
Typically, patients would require up to six months of DAPT after a PCI procedure with a DES, but Rissanen offered examples of investigations that have pointed to the utility of a shorter duration DAPT strategy after DCB implantation. Occasions where this may be a useful approach include in the primary prevention of bleeding, or as a means of “secondary prevention” through early cessation of antiplatelets if bleeding occurs post-PCI, he said. Other strategies may include a single antiplatelet therapy (SAPT)-only approach, he added, something that may be necessary in patients requiring imminent urgent surgery.
More data on this topic are coming, and Rissanen later offered delegates details of the ongoing DEBATE study, comparing the use of SeQuent Please NEO or DES in the HBR patient population, as well as different antiplatelet treatment regimens. Investigators hypothesise that the DCB strategy coupled with a shorter regimen of antiplatelets will be non-inferior to DES treatment with a longer DAPT duration against a primary endpoint of major adverse cardiovascular events (MACE) and bleeding at 12 months in patients with stable or acute coronary disease. Currently, the multicentre, international trial has enrolled around 30% of patients, Rissanen revealed.
Complex lesions, bifurcations and more
For bifurcation lesions, Bimmer Claessen (Amsterdam UMC, Amsterdam, The Netherlands) argued that DCBs have been shown to lead to angiographically superior results in side branches compared to plain balloon angioplasty, commenting that it may be a suitable therapy where the operator is keen not to compromise the main branch. “DCBs are also great in small side branches,” he said, adding: “we need more evidence of an all-DCB approach in true bifurcation lesions and left main bifurcations”.
“In our daily life, we know that DCBs can work. We have very good experience with DCBs in complex lesions,” argued Florim Cuculi (Heart Centre Lucerne, Lucerne, Switzerland) in his presentation ‘Redefining indications for DCBs in CTO PCI’. Jiménez, meanwhile, put forward the case for the use of DCBs in the setting of diffuse disease. “Most of the current worldwide population does not die after the first ischaemic event, they survive, and they develop more complex and diffuse CAD over the years. We are going to have to deal with this in the cath lab,” Jiménez said. He pointed out that, presently, there are a lack of randomised trial data to underpin this approach, but said that DCBs alone, or alongside DES as a part of a hybrid strategy, are a safe and effective option in diffuse disease.
Robert Byrne (Royal College of Surgeons in Ireland University of Medicine and Health Sciences, Dublin, Ireland) offered insight into some of the key data shaping practice, demonstrating the performance of current technologies, and stressing that, as the most widely studied device to date, SeQuent Please NEO is positioned as the “gold standard” by investigators as the comparator device when studying DCB-PCI.
Among the early studies highlighted by Byrne was ISAR-DESIRE 3, which pitted the SeQuent Please against paclitaxel-eluting stents or balloon angioplasty alone. This showed that the paclitaxel-coated balloon has a similar revascularisation rate as the stent, but lower than balloon angioplasty. Ten-year results of the study, published in 2023, show that the results are sustained out to the long term.
More data on DCB outcomes and safety are anticipated in the coming years, with devices from several companies under investigation. At present, however, SeQuent DCBs remain the most-studied devices in use—with no evidence of a class effect across the available technologies.
Byrne picked out studies comparing SeQuent Please to competitor devices that include the recently-US Food and Drug Administration (FDA)-approved Agent DCB (Boston Scientific). In both the AGENT ISR trial from 2020 and the ISAR-DESIRE 3A trial from 2022 the SeQuent Please was shown to perform favourably in comparison to Agent.
Data from the TRANSFORM I trial were also shown, a trial that compared the SeQuent Please NEO to the MagicTouch (Concept Medical) sirolimus-coated balloon in the setting of de novo small vessel disease, with the investigational MagicTouch device failing to meet non-inferiority for the endpoint of angiographic net gain at six months in comparison to SeQuent Please NEO.
A further study of note is REFORM, comparing the Biolimus A9-coated balloon (Biosensors) to SeQuent Please, in which it was shown that the percentage in-segment diameter stenosis at six months was 41.8% with the Biolimus-coated balloon versus 31.2% for SeQuent Please, meaning that the Biolimus A9 balloon did not meet non-inferiority versus SeQuent Please.
“Large trials are needed to move the field along,” commented Byrne, singling out the REVERSE study as one that has “captured the imagination” among followers of DCB research. REVERSE, a randomised, open-label multicentre trial is enrolling 1,436 patients at centres in South Korea, Malaysia, Taiwan and Singapore, comparing SeQuent Please NEO to a current-generation DES for the treatment of large CAD with de novo culprit lesions—which is indicative of the move to establish DCBs in a wider range of indications, beyond ISR, where the therapy has typically been positioned. Enrolment in the trial is slightly ahead of expectation, Byrne noted, with more than 520 patients recruited as of August 2024.
Delegates heard how new data are shaping approaches to PCI in Europe and further afield. Claessen opened the session with an introduction to the DEBuT LRP trial, a study looking at changes in plaque characteristics after DCB usage in patients with acute coronary syndrome as measured by intravascular ultrasound (IVUS)-near-infrared spectroscopy (NIRS). The trial sought to assess the impact of paclitaxel-coated balloon treatment of lipid-rich plaques on the reduction of maxLCBI4mm—the maximum lipid-core burden index in a 4mm segment.
“Our goal is to achieve plaque stabilisation in a therapy where the benefits outweigh the risks,” said Claessen. DCBs may provide the best strategy in this setting compared to a permanent implant, Claessen said, as they can provide local delivery of the drug with minimal injury to the vessel, homogenously across the vessel.
The first-in-human, proof-of-concept study showed that use of the SeQuent Please NEO resulted in a significant reduction of maxLCBI4mm without eliciting any safety concerns. The concept will be explored further in the DELETE-LRP study, a randomised trial comparing the paclitaxel treatment of lipid-rich plaque versus control.
Takashi Ashikaga (Japanese Red Cross Musashino Hospital, Tokyo, Japan) shared insights from Japan, where he explained that DCBs have been in use for over a decade and detailed that around 20% of PCIs currently involve the use of DCB technology.
Controversies: Guidelines and trials
Though the field of DCB-PCI is rapidly evolving, it is not without controversies. Byrne offered an analysis on two developments from the recent 2024 ESC congress (30 August–2 September, London, UK), focusing on two areas: the release of new guidelines on the management of chronic coronary syndromes (CCS) prioritising DES over DCB for the treatment of ISR following PCI; as well as results of the REC-CAGEFREE 1 trial, in which DCB was found to be less effective than DES for previously untreated non-complex coronary lesions. “It’s fair to say that both of these came as a bit of a surprise,” Byrne said, reflecting the view of many proponents of DCB-PCI.
Byrne questioned whether the studies cited within the CCS guidelines reflected the best available evidence to elicit a change to recommendations for DCBs as a first-line treatment for ISR and commented that more evidence from investigational device exemption (IDE) trials taking place in the USA could help to change this picture.
Offering his critique of the randomised REC-CAGEFREE 1 trial, which compared the Swide (Shenqi Medical) DCB to the Firebird 2 (Microport) among 2,272 patients at 42 sites in China, Byrne expressed surprise at the outcome, and highlighted some of the limitations of the trial.
REC-CAGEFREE 1 did not meet its primary endpoint of reducing combined rates of cardiovascular events: cardiac death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularisation. And, patients who received the DCB were significantly more likely to experience a cardiovascular event after two years. Byrne said that the most important limitation of the study is a lack of knowledge of the relative performance of the investigational device, commenting: “the clinical performance of the study device remains somewhat unclear”.
Lesion preparation: Techniques and tools
Sessions also homed in on optimising the use of DCBs, with a focus on the role of imaging and physiology techniques and technologies, new devices in lesion preparation and antithrombotic regimens after DCB therapy.
“Lesion preparation is key for success,” Rissanen said. “In the past we have used angiographically based methods and maybe FFR [fractional flow reserve] in some cases, but now we are using more imaging, and this will be very important for the assessment of DCB cases in the future.”
Klaus Bonaventura (Ernst von Bergmann Klinikum, Potsdam, Germany) expanded on this point, explaining how lesion preparation is a key step for any PCI procedure—whether that involves the use of a DCB or other available devices—and considering the criteria for optimal lesion preparation. Cardiologists should consider all contemporary available tools in the cath lab when deciding on their approach, Bonaventura said, in a presentation in which he also considered the occurrence of intimal dissection, describing this as an outcome that should not be feared when adopting a DCB-PCI approach. The acceptable outcome of lesion dissection for DCB use should be a non-flow-limiting dissection with a residual stenosis of ≤30%.
Though not necessarily new, according to Jeger, tools including semi-compliant balloons, non-compliant balloons, scoring or cutting balloons, intravascular lithotripsy (IVL) or atherectomy all have a role in lesion preparation, depending on lesion characteristics and plaque composition.
“The plaques we encounter are not all similar. We have some soft plaques, some persistent plaques, there are sometimes some fibrotic lesions and some calcified lesions,” he said. “Depending on the enemy, you have to use different weapons.”
Non-compliant balloons might be deployed in uncomplicated lesions, for example, and these devices exhibit higher rates of angiographic success with lower rates of residual stenosis and high-grade expansions, Jeger detailed. Scoring and cutting balloons produce a controlled dissection and facilitate radially concentric vessel expansion.
Rotational or orbital atherectomy may reduce the rate of high-grade dissection, whilst IVL is used to modify softer plaque and shows similar vessel expansion in calcified lesions as compared to either atherectomy approach. “Stepwise escalation using different tools is the way to success,” Jeger commented.
Claessen, meanwhile, offered an overview of the latest advances in imaging guidance and physiology and their use in DCB-PCI. “We are in an era now where we have a lot of techniques that allow the use of physiology,” he said, touching on the growing number of physiology indices, which include computed tomography (CT)-derived FFR, angiography-derived FFR and wire-based methods including hyperaemic pressure ratio and non-hyperaemic wire-derived pressure ratios. All of these tools can aid lesion preparation by measuring flow status and predicting late lumen enlargement (LLE), he detailed.
Intravascular imaging, which includes technologies such as IVUS, optical coherence tomography (OCT), IVUS-OCT and NIRS-IVUS, meanwhile, can serve as useful options for lesion severity assessment, as well as providing anatomical guidance pre-, during, and post-PCI. “Contemporary PCI mandates the use of physiology and imaging, particularly in selected clinical scenarios,” Claessen told attendees in summing up his talk.
Coatings: Paclitaxel and sirolimus
Presenters also looked at technology and innovation in the DCB arena, with a focus on the differences in the drug coatings currently available in the market. Attendees heard how different coatings, dosage, excipients and coating procedures play a role in drug release, crystallinity and particle size, and how these factors influence drug bioavailability and persistence.
B Braun is presently the only provider with both paclitaxel- and sirolimus-coated balloons in its range, attendees heard—SeQuent Please NEO (paclitaxel) and SeQuent SCB (sirolimus). Both anti-stenotic drugs have been used extensively in the treatment of CAD since the beginning of the 21st century, though paclitaxel remains the most widely used drug for coronary DCBs, with balloons using sirolimus the most prevalent coating for DES technologies. The evidence base for the efficacy of sirolimus-coated balloons remains some way behind paclitaxel, though studies are ongoing. Taking the SeQuent DCB family of devices as an example; to date, there are more than 110 studies, including 35 randomised controlled trials, with a total of more than 25,000 patients having received the SeQuent Please NEO, as well as five randomised trials with 500 patients enrolled investigating the SeQuent SCB.
DCB Days attendees heard how both drugs elicit different properties, with paclitaxel taking less time to administer at the vessel wall. Additionally, paclitaxel is more lipophilic than sirolimus and has been shown to have a lower solubility in aqueous solutions (0.3µg/mL vs. sirolimus 2.6µg/mL). The mechanism of action between the two drugs also differs, as paclitaxel binds irreversibly to microtubule structures, whereas sirolimus binds reversibly to the mTOR-enzyme, making paclitaxel more persistent and able to remain in-situ for a longer duration.
As Alfonso commented, the availability of two different DCB coatings—paclitaxel and limus derivatives—may mean that “there is opportunity to be specific on using different drugs for different patient and anatomic subsets”.
Coatings: Data, drug delivery and physician preference
Bonaventura considered the relative merits of paclitaxel and sirolimus and the question of the ideal drug—highlighting the current disparity in data between the two agents. Due to the wide usage of sirolimus in DES platforms, and historic safety concerns over the use of paclitaxel-coated devices in the peripheral arteries—since allayed—there may be a “psychological” preference for this drug amongst some operators, he suggested, but more data will be crucial to determining its role alongside the established paclitaxel in DCBs.
Jiménez highlighted the concerns regarding the challenge posed by sirolimus-coated balloon technology in effectively delivering sirolimus to the vessel wall and ensuring its sustained presence over time. He addressed these doubts with a series of documented cases with sequential OCT imaging, demonstrating the presence of the drug in the arterial wall after DCB-PCI with SeQuent SCB, as well as its persistence weeks later. These findings were accompanied by excellent angiographic and clinical outcomes. “These are results we consistently observe in cases where we use SeQuent SCB alongside intracoronary imaging,” Jiménez stated. These are very intruiging data, and we are progressing with a study in this direction to better understand these findings and establish their relationship with optimal long-term patient outcomes.”
Cuculi offered insights into the use of the SeQuent SCB—“the new kid on the block”—in a real-world setting, summarising some of the cases and published data for the device from his centre. “Classic” cases for using the SCB might include a CTO, where the presence of diffuse disease means there is no option to use a stent, calcified lesions, or instances where a reduction in antithrombotic therapy may be appealing.
Though there are promising signs for the safety and efficacy of some sirolimus-coated balloons, including the SeQuent SCB, at present, there are very limited clinical data, Bonaventura went on to note, with no indication of a clinical advantage of sirolimus over paclitaxel, which has proven safety and efficacy. More data and experience of the efficacy of the available sirolimus-coated devices are needed, he said, commenting that many interventionalists will need this to build up trust in the use of these devices. “For those who already have trust in sirolimus-coated balloons, this may be an alternative to work implant-free if data on selected sirolimus-coated balloons confirm at least non-inferiority to established paclitaxel-coated balloons,” he concluded.
“It is great to see that the DCB technique is gaining momentum,” Jeger told Cardiovascular News, reflecting on the outcomes of the event. “We know from lots of trials and lots of experience in clinics that the technique works, and we want to show how you can use these devices and how you can trust in the technique. The DCB is here to stay, and we know it will be an important add-on to current interventional techniques.”
Watch a full video recap here.
