DCB in PCI: Adjunctive therapy or standard of care?

May 2022 | Educational Supplement

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DCB in PCI: Adjunctive therapy or standard of care?

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DCB story Contents:

2-3 The story of the DCB

4-5 Indications for

coronary DCBs

6-7 The role of vessel preparation

Drug-coated balloons: The story so far Bruno Scheller (University of Saarland, Homburg/Saar, Germany), a pioneer of drug-coated balloons (DCBs), discusses the origins and science behind the technology, the important clinical data underpinning DCB use in the coronary arteries, and current treatment indications.

SCHELLER IS A FAMILIAR FIGURE to the global interventional cardiology community, largely thanks to his work in developing DCB technology in the late 1990s, when he worked alongside Ulrich Speck (Berlin, Germany). The two were the first to prove the concept of the DCB, and led the first clinical trials to demonstrate the safety and efficacy of the technology.

The history of the technology can be traced back to the late 1970s with the development of balloon angioplasty led by Andreas Grüntzig (Zürich, Switzerland).

Then, since the early 2000s, drug-eluting stents have become a mainstay technology for percutaneous coronary intervention (PCI). “In the peripheral arteries the DCB has become a mainstream therapy, but in the coronary arteries the field is dominated by drug-eluting stents,” comments Scheller.

Scheller adds that the idea of “leaving nothing behind” by using a DCB is very attractive, especially in younger patients or those with long lesions. “If you have an acceptable result, without flow-limiting dissections, you can expect that your vessel will look better after several months and you avoid all the long-term effects that you have with a permanent implant, and that is the beauty of this therapy,” he comments.

In essence, the DCB is a semi-compliant balloon coated with an antiproliferative drug—chiefly paclitaxel—which is transferred to the vessel wall when the balloon is advanced and expanded into the artery. This is seen as offering some advantages compared to using a drug-eluting stent, in particular due to not requiring the presence of a permanent metal or polymer structure, which may cause an inflammatory response, or as an alternative option in cases where stent implantation may be technically challenging. The concept of “leaving nothing behind” is why the DCB continues to

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emerge as an increasing area of interest in interventional cardiology.

Considering the use of a DCB when compared against a drug-eluting stent, he comments that there are two scenarios to be considered. The first, which is the widelyaccepted indication in current guidelines, is the treatment of in-stent restenosis. “In this situation the big advantage of the DCB is that you avoid another layer of metal, and we know very well that the more metal you have there, the more coatings on the stent you have that may induce inflammation, additional injury and so on,” Scheller notes.

A challenge with treating in-stent restenosis, he says, is that there is “negative selection” based upon the fact that the patient has already been treated with a drugeluting stent and has nonetheless developed restenosis. Furthermore, in-stent restenosis is often associated with mechanical issues, such as the presence of a poorly expanded stent, which may require more structural support.

“With the DCB you do not have the support of the second stent, and this means that you have to be more careful in terms of lesion preparation, when using a DCB, than when using a second stent. This also explains why, in some of the trials, repeated target lesion revascularisation was higher with the DCB compared to stent-in-stent,” he says.

Turning to de novo lesions, Scheller comments that there are specific circumstances when a DCB may be considered, but notes that for most interventional cardiologists being trained in primary stenting a drug-eluting stent is likely to be the favoured approach, as currently recommended in guidelines. “If you use DCBs in de novo disease, the DCB is only the last part of your procedure, and normally the easiest part of the procedure. The lesion preparation is much more important in the beginning,” he says.

8-10 Safety and efficacy

“Even if you have been trained to predilatate a lesion before you stent, it is a different approach if you prepare the lesion to decide whether you need to stent or if you can use only a balloon.” Preparing the lesion using the DCB-only approach requires the clinician to be “much more focused on achieving the best possible angioplasty result,” he explains.

While paclitaxel remains largely the coating of choice for DCBs in the coronary arteries, alternatives including limus drugs, which are used more commonly with drug-eluting stents, have been explored to assess efficacy.

Scheller explains that the use of limus on a balloon is far more complicated than when it is used on a stent as a stent platform can guarantee the controlled release of the drug in the tissue to allow for long therapeutic levels of the drug. But, in the case of balloon application, it is necessary to allow for a longer persistence of the drug to guarantee a therapeutic effect. This may be easier with paclitaxel as there is irreversible binding of the drug to the microtubes in the cell, whereas limus and its analogues have reversible binding to the mTOR receptor.

Scheller believes interventional cardiologists can be reassured of the safety and efficacy of paclitaxel-coated DCBs in the coronary arteries following the 2020 publication of a meta-analysis in in the Journal of the American College of Cardiology (JACC), of which he was a lead author, taking data from 26 randomised controlled trials, which reached the conclusion that paclitaxel DCBs for treatment of coronary artery disease was not associated with increased mortality. Indeed, there was evidence for the less frequent occurrence of hard clinical endpoints with paclitaxel DCBs. In terms of the clinical research of DCBs in de novo coronary lesions, Scheller points to BASKET-SMALL 2 as the biggest randomised trial in this space so far and one which is likely to influence future decision-making.

The multicentre, open-label, randomised non-inferiority BASKET-SMALL 2 trial compared 758 patients with de novo lesions less than 3mm in diameter, receiving either a DCB or a drug-eluting stent. Carried out

by Raban Jeger (University Hospital Basel, Basel, Switzerland) and colleagues, the study’s primary objective was to show noninferiority of the DCB versus the drug-eluting stent regarding major adverse cardiac events May 2022

DCB in PCI

If you have an acceptable result, without flowlimiting dissections, you can expect that your vessel will look better after several months and you avoid all the longterm effects that you have with a permanent implant, and that is the beauty of this therapy” Bruno Scheller

(MACE) which included cardiac death, nonfatal myocardial infarction, and target-vessel revascularisation after 12 months.

Published in The Lancet in 2018, results from the trial showed the non-inferiority of the DCB versus the drug-eluting stent, with similar levels of MACE (7.5% for the DCB group vs 7.3% for the drug-eluting stent group, hazard ratio [HR] 0.97 [95% CI 0.58–1.64], p=0.9180) between the two groups. “I think this is a landmark trial and I hope that it will influence the next version of the guidelines which state at this time that there is no evidence for de novo disease with a DCB,” says Scheller, commenting on these data. “I think that BASKET-SMALL 2 should contribute to change this recommendation.”

Another important trial highlighted by Scheller is DEBUT, which investigated the use of DCBs for treatment of de novo lesions May 2022

in patients with high bleeding risk. Performed at five sites in Finland, the randomised, single-blind non-inferiority trial hypothesised that PCI with DCBs would be non-inferior to bare-metal stents for this patient population.

A total of 208 patients were enrolled in the trial, which reported that at nine months MACE had occurred in one patient (1%) in the drug-coated balloon group and in 15 patients (14%) in the bare-metal stent group (absolute risk difference −13.2 percentage points [95% CI −6.2 to −21.1], risk ratio 0·07 [95% CI 0.01 to 0.52]; p<0.00001 for non-inferiority and p=0.00034 for superiority).

Though the number of patients treated in the trial is small, Scheller believes that the findings may be significant. “If you look at the total event rates, which are close to 0 for DCBs in high bleeding risk patients, I think this is very impressive. Therefore this

is another important trial because it points to the patients that may benefit from DCBs.” Taking these two trials together, Scheller comments, “These trials point to the direction of de novo small, and de novo high bleeding risk, and that these may be the fields to go.”

Further research is particularly important, according to Scheller, in the treatment of bifurcation lesions using a DCB. “The DCB approach for bifurcations is completely different to current recommendations on bifurcation treatment. The approach for DCBs is: prep the main branch, prep the side branch, deliver the drug to the side branch, forget the side branch and treat the main branch,” he explains. “This strategy is totally different and it will be interesting to see how we answer the question ‘what is the better for bifurcations—full metal jacket or as little metal as possible in a randomised trial?’”

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DCB indications

Existing and emerging indications for coronary DCBs Drug-coated balloons (DCBs) have become an important alternative to stent placement in certain situations such as the treatment of in-stent restenosis, addressing small coronary artery disease, and increasingly in other instances where a “leave nothing behind” approach may also be beneficial. Flavio Ribichini (University of Verona, Verona, Italy) discusses some of the existing and emerging indications for coronary DCBs, as well as the developing understanding of the potential role of the technology.

“THIS IS A CONCEPT I REALLY LOVE,” says Ribichini, referring to the theory of leaving nothing behind in a vessel—which he describes as the one major step forward to influence thinking within percutaneous coronary intervention (PCI) in the last 20 years. “The idea of restoring a normal vessel lumen, without leaving a permanent prosthesis is ideal under a biologic standpoint, to say it in a simple way,” he explains. “Why is that? Because, we know that atherosclerosis is a progressive disease and that especially in young patients, it may not be solved with one procedure.

Importantly, an initial treatment should not preclude future therapeutic interventions”

Vessel restoration: A concept gaining momentum

An ageing population presents the potential for patients to require multiple opportunities for coronary interventions, Ribichini argues, pointing out that this is one of the benefits of seeking to leave nothing behind in the vessel.

“People born in this new millenium have a life expectancy of around 100 years. If they have their first coronary event in their early forties, they may have another 60 years ahead when they could face problems related to the progression of the vascular disease .

“Currently, we rely on very good metallic stents with benign polymers and effective antiproliferative drugs. Using these, we can manage ischaemic heart disease for at least three to five years,” he adds. “But, we know that the efficacy of PCI is inferior to that of surgery in the long term. Indeed, stents do not address the issue of atherosclerosis progression, stents can stimulate neoatherosclerosis at long term, and can even fracture, reducing the real efficacy of PCI over time with a high incidence of ischaemic recurrences after five years of stenting”.

The concept of restoring the artery wall structure and function without leaving a

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permanent prosthesis in the vessel first gathered momentum with the emergence of bioresorbable vascular scaffolds (BVS), which were designed to overcome some of the limitations of drug-eluting stents, but ultimately failed to gain traction. “Ideally, the concept of a BVS is that of restoring the vessel lumen, to get rid of the plaque by the delivery of anti-atherosclerotic drugs that also act as antiproliferative agents that prevent post-PCI restenosis and allow the re-

growth of a normally functioning endothelial coverage,” comments Ribichini.

Presently, DCBs are recommended as the treatment of choice for in-stent restenosis linked to drug-eluting or bare metal stents, while for de novo coronary lesions, the application of DCB treatment is limited to conditions such as small vessel disease, where prospective single-arm trials, retrospective and observational cohort studies, and registries have shown that paclitaxel DCBs can safely and effectively treat these lesion types.

In-stent restenosis is different from restenosis after angioplasty as stent implantation eliminates vessel recoil but increases the extent of neointimal hyperplasia. In-stent restenosis is a relatively routinely observed indication, with studies in Europe and the USA estimating that it can occur in around 5‒10% of PCI cases.

The third report of the International DCB Consensus Group, published in the Journal of the American College of Cardiology (JACC) in 2020, notes that good candidates for DCBs may include those with a first instent restenosis, those with multiple previous stent layers, patients in need of a shorter dual antiplatelet therapy (DAPT) duration, or

The idea of opening a vessel, without leaving a permanent prosthesis is biologically correct, to say it in a simple way” Flavio Ribichini

May 2022

DCB in PCI

with relevant side branches emerging from the in-stent restenosis. Ribichini points out that the use of a DCB for the treatment of in-stent restenosis is backed by the highest level of evidence (A), making it a Class I recommendation. Discussing the decisionmaking process facing the operator in these cases—whether to opt to re-stent the patient or to move ahead using a DCB—he offers the view that a DCB is often preferable, commenting: “delivering an anti-restenotic drug locally to mitigate excessive neointimal growth within a stent is the most logical therapeutic approach if the previously implanted stent shows no mechanical issues.

From my point of view: If a well deployed drug-eluting stent fails, the operator should question if there is something wrong with this patient. Indeed, some patients do react to having foreign bodies, by developing aggressive neointimal proliferation,” he adds.

“These patients are ideal for DCBs and I think are bad candidates for a recurrence of the same problem with the same technology.”

The evidence for DCB treatment of in-stent restonsis

The International DCB Consensus Group notes that patients with in-stent restenosis after the implantation of a drug-eluting stent represent a selected high-risk population, and the potential relative efficacy of DCBs versus drug-eluting stents according to the underlying tissue substrate—neointimal hyperplasia versus neoatherosclerosis—may be different. On this point, Ribichini adds: “If you have neointimal tissue and your old stent is well expanded and is not fractured then DCBs should be the therapy. If the stent is under-expanded, or just crushed because of a heavily calcified arterial wall, the implantation of another stent may be necessary to gain an acceptable lumen area.

However, such a decision can be taken only after an accurate intravascular observation by using intravascular ultrasound (IVUS) or optical coherence tomography (OCT), as recommended by international guidelines”.

Indeed, the use of intravascular imaging modalities is strongly favoured in order to guide much better decision-making, whether that be in cases involving the use of a DCB or when using a second stent.

Arguing in favour of a “leave nothing behind” approach to the treatment of in-stent restenosis, Ribichini says: “If you put a second layer of stent in it, the residual lumen gets smaller and smaller, that is also the advantage of treating small vessels with a DCB in the first instance, not with a stent.

The stent always cages the vessel, it is always smaller than the native vessel, and so you are making this lumen smaller and smaller.”

May 2022

We started with balloons with high rates of recoilrelated restenosis.

Bare metal stents were better but still had frequent restenosis related to excessive neointima.

Drug-eluting stents are very effective, but remain a permanent and unnecessary foreign body that may induce neoatherosclerosis and compromise future repeated interventions. The only step forward is restoring the vessel wall, leaving nothing behind” Flavio Ribichini

Regarding native vessels, two clinical trials comparing drug-eluting stents and DCBs for the treatment of small-vessel coronary artery disease (defined as lesions in vessels ≤2.75 or <3mm)—BELLO and BASKET-SMALL 2—highlight the promise for the use of DCBs in this indication. BELLO, results of which were published in JACC in 2012, showed that the use of a DCB appears to be associated with lower incidence of major adverse cardiac events (MACE) when compared with drug-eluting stent treatment at three years in small coronary vessels. Results of BASKETSMALL 2, subsequently published in The Lancet in 2018, showed non-inferiority of the DCB versus the drug-eluting stent regarding MACE after 12 months. Ribichini notes that there is reliable evidence that the elution of paclitaxel on the native vessel walls is anti-restenotic, adding that the rate of recurrence after the elution of paclitaxel in a native vessel wall is “more or less the same as you would expect if you implant a newgeneration drug-eluting stent”.

DCBs as an alternative option in native vessels

Taking all of this evidence together, the International DCB Consensus Group concludes that although DCBs are an established therapeutic option for the treatment of in-stent restenosis supported by guideline recommendations, a DCB-only approach in de novo lesions of coronary small-vessel disease is now a valid treatment alternative to drug eluting-stents.

Turning to high bleeding risk patients, Ribichini says that DCBs may offer a good alternative to using longer stents, for example, commenting that there is a “direct relationship between the length of the metal and the failure of the stents”.

“If you are planning your strategy, and you start thinking to implant 5cm of stents, or even more, yours is not a good elective strategy,” he says. “It might be necessary in an emergency, but it is not plan A, it is not the best treatment, especially in young patients with long life expectancy.”

Secondly, he says, if the vessels are relatively small, DCBs may be a viable alternative, as another variable that correlates with bad outcomes is the stent diameter. “This is why we think about DCBs as a good option for long lesions and small vessels. But it is intuitive to think that, if it works in small vessels and long lesions, it will certainly work even better in big vessels”. The main barrier for accepting DCBs as an alternative to stents, especially in large vessels, is the angiographic appearance of the immediate result (which is hardly “stent-like”), with more residual stenosis and dissections, therefore looking “worse” in aspect compared to stents, but what should really count is the clinical result and not the aspect. Nevertheless, it is needless to say that adequate vessel preparation is key, regardless of the final treatment strategy, and that in cases of severely calcified arteries or when abrupt vessel occlusion occurs, stenting remains the sole option.

In summary, Ribichini repeats his view that DCBs revitalise the fascinating concept of achieving percutaneous revascularisation without permanent “caging” of the vessel wall whenever possible, noting that the technology has potential to address some historical drawbacks of PCI. He says: “We started with balloons with high rates of recoil-related restenosis. Bare metal stents were better but still had frequent restenosis related to excessive neointima. Drug-eluting stents are very effective, but remain a permanent and “unnecessary” foreign body that may induce neo-atherosclerosis and compromise future repeated interventions.

The only step forward is restoring the vessel wall, leaving nothing behind.”

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Vessel preparation

Be prepared: Why vessel preparation is fundamental to DCB outcomes Achieving adequate vessel preparation is fundamental to optimising outcomes in patients undergoing percutaneous coronary intervention (PCI) using a drugcoated balloon (DCB). This is among the important messages from Azeem Latib (Montefiore Medical Center, New York, USA) and Azfar Zaman (Freeman Hospital and Newcastle University, Newcastle-upon-Tyne, UK) who discuss the potential benefits of a “leave nothing behind” approach to PCI, how to know when sufficient vessel preparation has been achieved, and what to expect when using DCB in coronary arteries.

THE CONCEPT OF LEAVING NOTHING behind in the artery leaves open the possibility for treatment of the vessel at a future timepoint, which was something that was particularly appealing with a bioresorbable vascular scaffold (BVS), according to Latib. However, he notes that the devices had limitations, including that they were bulky, they started crumbling and dismantling, and they caused stent thrombosis. “It created for the larger community the idea that leaving nothing behind is appealing,” he comments. “So now, people have thought that they do not want to leave anything behind, but we do want to give a drug to the artery. Could DCBs allow us to do that? I have certainly seen the biggest increase in usage of drug-coated balloons after BVS was taken away,” he adds.

An important point to consider, according to Zaman, is the role of the DCB—chiefly that of delivering a drug to the vessel.

“Before thinking about getting to the DCB, we have to first treat and prepare the lesion.

It is important to remember that the DCB is essentially only used for drug delivery.

If one remembers that, then the rationale for adequate lesion preparation before drug delivery becomes easy to understand.”

Considering the importance of lesion preparation, Latib comments that it is key to consider the role of the DCB in the first place. “The first thing physicians need to understand is the fact that we are talking about a drug-coated balloon,” he says. “A lot of thought actually went into the whole definition—it is not a drug-eluting balloon, it is a drug-coated balloon. It has a drug coating on it that is going to be transferred to the wall when the balloon is inflated. So, when I think of a drug-coated balloon, it is the last thing I do to the artery.”

Zaman continues that an important outcome of vessel preparation should be

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the achievement of a residual stenosis of less than 30%, which can be reached using “whatever tools we have to hand to achieve that”. “Whether that is starting with a noncompliant balloon, and progressing to scoring and/or cutting balloons, all of these tools should be used, and the very last goal is to

If you can show with intravascular analysis that you have achieved a plaque area of less than 30% this is the ideal preparation for the lesion” Azfar Zaman

deliver the drug on the drug-coated balloon,” he says.

Latib adds that there are other important considerations when determining adequate lesion preparation. “Lesion preparation for me means a couple of things,” he says.

“It means treating the stenosis so that we have a minimal residual stenosis, at least less than 30% residual stenosis. We have TIMI [thrombolysis in myocardial infarction score] 3 flow, and there is no flow-limiting dissection.”

According to Latib, these are three minimum criteria that can be accepted to have done good lesion preparation. “The way we do the lesion preparation really depends on the type of lesion,” he continues.

“Is there calcium, is there lipid, is there fibrotic tissue? Those are basically the three categories,” explains Latib. Use of intravascular imaging, either intravascular ultrasound (IVUS) or optimal coherence tomography (OCT) helps to determine the strategy. “Based upon what I will find, I usually will ask—can I use non-compliant balloons versus needing to use a speciality balloon first, whether that is a cutting balloon, scoring balloon or very high pressure balloon, or is it a lesion where I need to use some sort of atherectomy device?”

Different types of lesion require different approaches, and different treatment algorithms to meet the end goal of adequate preparation. According to Latib, there are a number of important considerations dictating which tools should be used depending on the type of plaque being treated. “If it is a lipidrich plaque, maybe just balloon angioplasty is good enough,” he explains. “If it is fibrotic then maybe we need to add using a speciality balloon—whether that is a cutting balloon or a scoring balloon.”

If the vessel is calcified, the physician should consider whether they need to employ atherectomy, cutting balloons, or potentially lithotripsy to prepare the lesion and achieve the goal of less than 30% stenosis, TIMI 3 flow, and no flow-limiting dissection.

Latib continues: “Whenever we do this, there is always some dissection, so that is for me what lesion preparation means. It means looking at the lesion, deciding what device I need to get those three factors and then doing that. It also means, once I have treated the lesion, reassessing it to see if it does meet those criteria.”

Both Zaman and Latib note that use of IVUS may be fundamental to adequately assessing whether satisfactory lesion preparation has been achieved.

“Typically, it has been [performed with] angiographic assessment, but ideally, we should use an imaging modality such as May 2022

DCB in PCI

intravascular ultrasound,” says Zaman. “If you can show with intravascular analysis that you have achieved a plaque area of less than 30% this is the ideal preparation for the lesion.”

Similarly, physiologic assessment such as fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR) may be options for assessing the outcome of lesion preparation. However, Zaman and Latib both note that there is less certainty around how this should be viewed.

Zaman comments: “There are no studies to support the use of FFR in patients in whom you wish to deliver DCBs, but if you wish to use FFR to achieve an outcome that shows an FFR of above 0.8 (iFR >0.9) then my feeling is that if you can achieve that then it will be a good outcome for the patient.”

“We do not fully understand what a good result is when you are only doing ballooning,” adds Latib. “But basically, if you are going to do FFR, and you can get an FFR that is above 0.8, I think people will feel that they have done a good job and they have a good result.

“It may not be perfect, but it is better than it was before. Many people who are using FFR will measure it before they do lesion preparation and then after, and if they have shown a suitable increase it is reassuring.”

In terms of the significant literature concerning DCBs in the coronary arteries, Latib points to the publication of a meta-analysis in 2020 in the Journal of the American College of Cardiology (JACC), authored by Bruno Scheller (Saarland University, Homburg/Saar, Germany) et al, documenting the survival after coronary revascularisation with paclitaxel-coated balloons.

Incorporating data from more than 4,500 patients enrolled in 26 randomised controlled trials between 2006 and 2019, and comparing DCB treatment to non-DCB devices such as conventional balloon angioplasty, bare-metal stents and drug-eluting stents, the analysis found that the use of paclitaxel DCBs for treatment of coronary artery disease was not associated with increased mortality.

“If anything, the event rates are slightly lower compared to stents,” he comments, adding: “Clinical events are important to patients. They care about dying and having a heart attack.”

In terms of the technical competence needed to perform lesion preparation prior to PCI using a DCB, Latib says that the techniques are easily learned by the majority of interventional cardiologists.

“It will take a little bit of adjustment but these are not difficult to learn,” he says. “They are easy techniques to learn, it just requires us to go a little out of our comfortable space and to try something new.

“The younger group of interventional cardiologists are really going to pick this up, May 2022

If I think about what is exciting in interventional cardiology, it is DCBs” Azeem Latib

and I think there are a couple of reasons why: They are already doing things better than I was doing when I came out of my fellowship. The younger generation is using a lot more imaging, because they want to understand their lesions better. They like this concept of leaving nothing behind, it is very appealing to them.”

Both Zaman and Latib say DCBs provide an important tool in the interventional cardiologist’s arsenal for select cases in which leaving nothing behind is a desirable objective.

“Stents that we have now are hugely successful and will continue to bear the great burden of PCI,” says Zaman. “What we can say is that there are a proportion of cases where DCBs offer the clinicians an option instead of drug-eluting stents.”

Zaman explains that whilst drug-eluting stents are effective at dealing with acute closure, they leave the potential to have stent thrombosis further down the line. “So, the concept of leaving nothing behind is attractive to patients and clinicians because you do not leave the metal cage behind and it allows the vessel, a) to recover function, and b) you do not have a late risk of stent thrombosis,” he comments.

Latib notes further that the development of the BVS in the late 2000s reignited an

interest in the 'leave nothing behind' concept, though ultimately BVS technology was withdrawn from the market.

“This gave us three things that will have changed practice forever, even though the technology is not here,” says Latib. “One is the concept of leaving nothing behind in the artery and how potentially appealing that is,” he explains. “The second thing they left behind was the whole concept of lesion preparation, and the third is intravascular imaging—even with metallic stents we were seeing data that we had never seen before.”

Furthermore, Latib describes the reemergence of DCBs as an exciting area of development within the specialty. “If I think about what is exciting in interventional cardiology, it is DCBs,” he remarks. “It is weird for me to say that, because I have been using it for such a long time! In the USA, I do not have it available commercially—I am involved in clinical studies—but in Europe, before, I was using it in probably 20% of my cases.

“I am so excited that something I have believed in for such a long time finally is getting the attention it deserves, because I think this technology is very innovative, and if we use it properly can overcome some of the limitations of stents.”

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Safety and efficacy

The importance of lesion preparation and its impact on long-term safety and efficacy for DCB treatment of de novo coronary artery disease “What I would urge you to consider when you are learning about drug-coated balloons (DCB), is that when faced with a coronary stenosis, you do not have to define whether you are going to put a stent in or use a DCB up-front,” says Darren Mylotte (Galway University Hospitals, Galway, Ireland). His view is that vessel preparation, or “physician preparation”, is an important concept to consider when choosing whether or not to opt for a DCB strategy for de novo lesions.

“You can prepare the lesion appropriately and then decide: stent or balloon? It is in either case very important to prepare the lesion, especially when considering a DCB, as unlike with stents, we have the issue of mechanical or elastic recoil.”

Simple de novo lesions

In simple de novo lesions, Mylotte says, a typical approach when considering a DCB involves the use of a coronary vasodilator or intracoronary imaging to appropriately size the vessel and then to perform predilatation using a balloon—more often than not a semicompliant balloon sized 1:1 to the vessel.

“If in doubt about the vessel diameter, one can start with a smaller balloon and then increase balloon diameter as appropriate,” adds Mylotte. “In terms of balloon length, the predilatation balloon should be as short as possible, since the DCB will need to be a little longer to ensure the proximal and distal edges receive drug therapy.”

If predilatation is not perfect, Mylotte says that the use of non-compliant, cutting and scoring balloons, sized 1:1 to the vessel, should also be considered. “You always have the option to switch strategy and to use a stent if you develop a concerning dissection after vessel preparation,” he adds. “If, however, you do not prepare properly, then you are unlikely to get a good result from the DCB in the first place.”

Complex lesions

Comparing the approach in more complex lesions, once again a vasodilator should be used in all cases, Mylotte says, and operators should be “more liberal” in their use of coronary imaging. “We want the proximal and distal vessel dimensions, and to understand the extent and location of calcification. After preparation we want to be sure that we have effectively fractured the

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calcium arcs,” he says. This would usually be achieved with non-compliant balloons, but using cutting or scoring balloons, lithotripsy, or other tools such as atherectomy, may be needed to prepare calcified vessels. Again, he repeats the point that the operator can choose to deploy a stent instead of using a DCB if concerning dissections occur during preparation.

Furthermore, with complex lesions is it also necessary to consider DCB delivery and transit time, Mylotte explains. “If you are delivering a DCB to a distal vessel with a lot of calcium proximally, you do not want to try and deliver the DCB, and then realise that it

is not possible to deliver these more bulky balloons. In more complex lesions, therefore, one should consider guide support, buddy wires, or guide extension to make sure of a relatively rapid transit time,” he explains.

It is necessary to assess whether lesion preparation for DCB is adequate: full expansion of the balloon with a 1:1 ratio; a ≤30% residual stenosis; absence of any flowlimiting dissections (Type A or B dissections are considered acceptable); and Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow, are the parameters of note.

When weighing up a DCB-led approach, Mylotte argues that it is important to consider the data regarding the safety and efficacy of the strategy.

Starting with safety, Mylotte says that, ultimately, “we are talking about dissections”.

“We need to get comfortable with the classification of dissections and understand the evolution of these dissections,” he explains.

Dissections

For Type A and type B dissections, Mylotte advises that these are, “essentially small areas of haziness or a linear dissection that are not associated with any contrast staining outside of the lumen, and not associated with ECG [electrocardiogram] changes or slow blood flow”. These dissections very rarely cause problems, he says, and can “comfortably be left in the DCB world.”

Type C dissection, where there is some staining outside the vessel lumen, is more contentious, says Mylotte. “Some operators are comfortable with these while others are more cautious and switch to a stenting strategy. I think it depends upon where you are in your DCB journey,” he reflects. “If you are starting, I would cover these with

We need to get comfortable with the classification of dissections and understand the evolution of these dissections” Darren Mylotte

May 2022

DCB in PCI

Bail-out stenting

20% Bello

2%

Abrupt vessel closure

Myocardial infarction

11%

1%

5.5%

Pre-stent era

DCB

DES

Debut

Post-stent era

<1%

0%

6%

14%

0-1%

2%

4%

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a stent, and if you are more experienced with this technology, then I think it is more open to interpretation.” For Type D or spiral dissections, Type E with intraluminal filling defects, or Type F where the vessel is closed, these clearly should not be left untreated, and the operator should then opt to switch to a stent strategy.

Mylotte goes on to discuss dissections that are being “left behind”, citing an important 2015 paper by Bernardo Cortese (AO Fatebenefratelli, Milan, Italy), published in JACC: Cardiovascular Interventions, which sought to understand the clinical and angiographic outcomes of dissections left after DCB angioplasty.1 “This is a really important paper,” says Mylotte, explaining that in the report, Cortese et al analyse 156 patients who received a DCB. Of these, 52 had a final dissection, of which four required stent implantation. The remaining 48 had angiographic follow-up at six months.”

“In this analysis, 45 of the 48 patients (94%) had complete healing of the dissection by six months, three (6%) had uncomplicated unhealed dissections,” says Mylotte.

He explains that there was no observed difference in major adverse cardiovascular events (MACE) between patients with a May 2022

DCB

DCB

dissection and those that did not have a dissection. “Just because you get a dissection with your DCB, does not mean you have to treat it with a drug-eluting stent,” says Mylotte, reflecting on the important message from this analysis. “If it is a Type A or Type B, you have a good safety profile.”

What I would urge you to consider when you are learning about DCBs, is that when faced with a coronary stenosis, you do not have to define whether you are going to put a stent in or use a DCB up-front”

DCB

DES

DES

Bail-out stenting

What is the requirement for bail-out stenting?

“That depends on the patient population, the types of lesions you are treating, and on your own experience,” he notes. Three trials, he reports, are important in this regard— BELLO2, DEBUT3 and BASKET-SMALL4.

In these trials 20%, 2% and 14% of patients, respectively, transitioned from an up-front DCB strategy to a stent strategy. “Therefore, in the region of about one-fifth, or a little less, will ultimately need a stent when you go down this route,” summarises Mylotte.

These trials also offer some reassurance over abrupt vessel closure. “In the pre-stent era, the risk of abrupt vessel closure, was about 11%,” explains Mylotte. “We certainly cannot accept those results in contemporary practice. In the post-stent era, abrupt closure occurred in less than 1%, and in the DCB era the reported rates are 0‒1%—that is because we understand how to prepare these vessels, the antiplatelet therapies are more potent, we check ACT [activated clotting times] in our cath lab, and we understand which dissections require a stent. Imaging and modern tools help us to get a good outcome.”

Looking at MI rates at between six and 12 months, Mylotte comments that these favour

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R R P

Safety and efficacy

P

P

S D

R A O

DCBs over first-generation drug-eluting stents or bare metal stents. In BELLO, the rate of MI after six months was 1% for DCB compared to 5.5% for drug-eluting stents; these rates were 0% for DCB compared to 6% for bare metal stents at nine months in DEBUT, and were 2% vs. 4% in favour of DCBs over first-generation drug-eluting stents at 12 months in BASKET-SMALL. “In terms of procedural safety, I think we are looking good,” remarks Mylotte.

Efficacy: A question of predilatation

Efficacy, Mylotte explains, comes down to getting a good predilatation. “That is to say, mechanical expansion, and then ensuring that we have good drug delivery.”

Mechanical expansion can be assessed using angiography, intravascular ultrasound (IVUS) or fractional flow reserve (FFR).

On drug delivery, Mylotte adds: “We need to make sure that we are efficient in terms of our handling of the balloon, that we do not touch the balloon itself, that we get it to the target quite quickly. If you have to pass

We have taken the first steps along this journey, but we have a lot more to learn with respect to the types of patient and lesions that could benefit from a DCB strategy” the balloon on multiple occasions you are going to lose a lot of the drug and have a suboptimal long-term result.“ Drawing again upon the BELLO, DEBUT and BASKET-SMALL data relating to target lesion revascularisation, Mylotte remarks that this is “really what efficacy is all about”.

In BELLO at six months, target lesion revascularisation stood at 4.4% in the DCB

arm vs. 7.6% in the drug-eluting stent arm; 0% vs. 6% in the DCB and bare metal stent arms in DEBUT at nine months; and 4% vs. 5% in BASKET-SMALL after one year.

“There is no suggestion that the efficacy of DCBs is lower than first-generation drugeluting stents or bare metal stents,” says Mylotte. Importantly, Mylotte reflects, “We do need data on how these devices compare to contemporary drug-eluting stents. We have taken the first steps along this journey, but we have a lot more to learn with respect to the types of patient and lesions that could benefit from a DCB strategy.”

References 1. Cortese B, Silva Orrego P and Agostoni P et al. 2015. Effect of Drug-Coated Balloons in Native Coronary Artery Disease Left With a Dissection. JACC: Cardiovascular Interventions, 8 (15), 2003–2009.

2. Latib A, Colombo A, and Castriota F, et al. 2012. A Randomized Multicenter Study Comparing a Paclitaxel Drug-Eluting Balloon With a Paclitaxel-Eluting Stent in Small Coronary Vessels. J Am Coll Cardiol, 60 (24), 2473–2480.

3. Cortese B, Silva Orrego P, and Agostoni, P, et al. 2015. Effect of Drug-Coated Balloons in Native Coronary Artery Disease Left With a Dissection. JACC: Cardiovascular Interventions, 8(15), pp.2003–2009.

4. Jeger, R, Farah A, Ohlow M. 2018. Drug-coated balloons for small coronary artery disease (BASKET-SMALL 2): an openlabel randomised non-inferiority trial. JACC: Cardiovascular Interventions, 8 (15), 2003–2009.

All rights reserved. Published by BIBA Publishing, London T:+44 (0)20 7736 8788, publishing@bibamedical.com.

The opinions expressed in this supplement are solely those of Medtronic and the featured physicians and may not reflect the views of Cardiovascular News.

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May 2022

*

†

1 2

S p U

B7606m

RIGHT CASE RIGHT TIME PREVAIL Prevail™ Paclitaxel Coated PTCA Balloon Catheter PUSHABILITY PUSHABILITY

210 106 Prevail DCB

RAPID ABSORPTION OF PACLITAXEL1

180

176

148

141

IN.PACT™ SeQuent®* Please SeQuent®* NEO DCB Falcon DCB Please DCB

FreePac™ coating combines two proven components that work together.5

Higher Is Better

PowerTrac technology and a hydrophilic coating facilitate superior deliverability and device performance.†2

Max Force Transferred (gf)

SUPERIOR DELIVERABILITY†2

™

AGENT™* DCB

Magic Touch™* DCB

Paclitaxel — potent antirestenotic drug that remains in tissue throughout the healing process6,7

Urea — biocompatible excipient that enables rapid drug delivery within 30–60 seconds1,3

EFFICACY

10 trials

> 1400 patients And confirmed in the PREVAIL Study4: . Includes complex lesions . 54.7% ISR . 79.2% small vessel in de novo lesions

* Third-party brands are trademarks of their respective owners. † Based on bench test data. Bench test data may not be indicative of clinical performance.

1 Prevail Instructions for Use. 2 Compared with IN.PACT Falcon DCB, SeQuent®* Please NEO DCB, Agent™* DCB, and MagicTouch™* DCB. Deliverability defined as pushability. Based on bench test data, 2020.

3 Barrett BJ. Contrast nephrotoxicity. J Am Soc Nephrol. August 1994;5(2):125-137.

4 Latib A, et al. PREVAIL Study, presented at PCR 2020, results through 12 months. IN.PACT Falcon DCB and Prevail DCB use the same FreePac™ coating. PREVAIL study did not have powered endpoints.

5 Virmani R. Arterial wall response to drug-coated balloons. Confluence. September 2016;13:15-19.

VERY LOW LATE LOSS IN ALL PATIENTS AT 6 MONTHS4 In-balloon Late Lumen Loss (mm)

As demonstrated in the EXCELLENT IN.PACT Falcon clinical SAFETYprogram: AND

Maximum acceptance rate 0.5 mm

0.12 ± 0.45 0.05 ± 0.44 All patients (N = 50)

6 Cremers B, Clever Y, Schaffner S, Speck U, Böhm M, Scheller B. Treatment of coronary in-stent restenosis with a novel paclitaxel urea coated balloon. Minerva Cardioangiol. October 2010;58(5):583-588.

7 PS762 preclinical study report: An Evaluation of the Medtronic Drug Coated IN.PACT™ Euphora™ Coronary Balloon Catheter in a Porcine Artery Model, 2016. On file at Medtronic.

-0.04 ± 0.41 de novo (n = 22)

ISR

(n = 28)

medtronic.eu/PrevailDCB

See the device manual for detailed information regarding the instructions for use, indications, contraindications, warnings, precautions, and potential adverse events. For further information, contact your local Medtronic representative and/or consult the Medtronic website at medtronic.eu.

UC202213556 aEE © 2022 Medtronic. All Rights Reserved. Not for distribution in the USA, France or Japan. 04/2022.

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RIGHT CASE RIGHT TIME PREVAIL Prevail™ Paclitaxel Coated PTCA Balloon Catheter

Prevail DCB offers the performance you want for treating complex lesions1:

. Superior deliverability — deliberately designed to maximise pushability . Rapid absorption of paclitaxel — facilitated by biocompatible urea excipient . Excellent safety and efficacy — demonstrated †2

1

3

in the IN.PACT Falcon clinical program; confirmed by the PREVAIL Study4

Third-party brands are trademarks of their respective owners.

Bench test data may not be indicative of clinical performance.

Prevail Instructions for Use. 2 Compared with IN.PACT Falcon DCB, SeQuent®* Please NEO DCB*, Agent™* DCB, and MagicTouch™* DCB. Deliverability defined as pushability. Based on bench test data, 2020.

3 Barrett BJ. Contrast nephrotoxicity. J Am Soc Nephrol. August 1994;5(2):125-137.

4 Latib A, et al. PREVAIL Study, presented at PCR 2020, results through 12 months. IN.PACT Falcon DCB and Prevail DCB use the same FreePac™ coating. PREVAIL study did not have powered endpoints. * †

1

See the device manual for detailed information regarding the instructions for use, the implant procedure, indications, contraindications, warnings, precautions, and potential adverse events. For further information, contact your local Medtronic representative and/or consult the Medtronic website at www.medtronic.eu.

medtronic.eu/PrevailDCB Europe Medtronic International Trading Sàrl.

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