Ready for the primetime? The future role of drug-coated balloons in PCI

“The evolution of PCI [percutaneous coronary intervention] has always been a continuum, with new devices addressing the limitations of previous devices,” Marie-Claude Morice (Institute Hospitalier Jacques Cartier, Massy, France) tells Cardiovascular News, discussing the growing interest in the use of drug-coated balloons (DCBs) in coronary interventions.

In the history of coronary interventions, this evolution has taken in coronary artery bypass graft (CABG) surgery, then balloon angioplasty, followed by bare metal stents, and later first- and secondgeneration drug-eluting stent (DES) platforms. “Now the drug-coated balloons are coming,” says Morice, commenting that these devices may address the limitations of even the best second-generation DES platforms. “It is now obvious that there are a few but unavoidable events that are occurring in the long term,” says Morice of the current-generation devices. Potential advantages of the DCB platform arise from the fact that there is no permanent implant left behind in the vessel after implantation, which can avoid some of the potential drawbacks of placing a DES, such as late stent thrombosis or in-stent restenosis.

Presently, DCBs are favoured in a subset of PCI indications, including the treatment of instent restenosis, where there are a wide set of data underscoring the safety and efficacy of such devices. The use of a DCB in this context carries a class I recommendation—with the level of evidence A—in guidelines from the European Society of Cardiology (ESC) and European Association for Cardio-Thoracic Surgery (EACTS). This recommendation is formed solely upon data from the PACCOCATH ISR I and II or PEPCAD trials which were performed in the majority using the SeQuent® (B Braun) family of devices. A key statement in the guidelines is that “a class effect for all DCBs cannot be assumed”— underscoring the importance of device selection based upon robust data.

“There is less but relatively strong evidence in small vessel native coronary artery disease,” adds Morice, discussing applications of the technology. “We all know that having those long lesions in small arteries treated by a full metal jacket leads to complications,” she adds. In this context, the BASKET SMALL-2 study is one such trial to have proven DCBs to be non-inferior to DES in native coronary lesions with a diameter less than 3mm, with the trial showing major adverse cardiovascular events (MACE) to be comparable between the two groups (7.5% for the DCB group vs. 7.3% for the DES cohort) after one year. However, larger trials are needed to confirm such finding, and they are ongoing.

Furthermore, Morice highlights bifurcation lesions as another indication in which the use of DCBs has shown to be a promising strategy. “We know that having two stents across a bifurcation is not ideal so interventional cardiologists are exploring drug-coated balloons in the side branch, or even the complete treatment of the bifurcation, in both branches,” she explains, caveating that this particular usage still requires further studies before it can be firmly incorporated into routine clinical practice.

Similarly, patients with a high risk of bleeding may also benefit from a DCB-only strategy, Morice comments, noting that this approach can facilitate a shorter course of dual-antiplatelet therapy (DAPT), a factor that was considered in the aforementioned BASKET SMALL-2, where patients with stable coronary artery disease received one month of DAPT, compared to six months for those patients who received stents. Further data on this topic come from the DEBUT trial, a single-blind, randomised, noninferiority trial examining the treatment of de novo coronary lesions in patients with high-bleeding risk using the SeQuent® Please DCB. Results from the trial, which were published in The Lancet in 2019, showed that the DCB was superior to stenting against a primary endpoint of MACE at nine months, with MACE having occurred in one patient (1%) in the DCB group versus 15 (14%) in the stent group.

To date, much of the evidence surrounding the safety and efficacy of DCBs centres on the use of paclitaxel-coated devices, but advances in sirolimusbased technology suggest that it holds promise as an alternative to paclitaxel for the treatment of both in-stent restenosis and de novo lesions. There is some evidence suggesting equivalency coming from 101 patients with in-stent restenosis randomised to SeQuent SCB or to SeQuent Please Neo, and another 70 patients with de novo lesions from a randomised trial conducted in Malaysia. Although the results are promising they must be confirmed in larger trials, Morice comments, adding that demonstrating the efficacy and safety of sirolimus-based platforms will be an important future area of study. “The evidence that we have at the moment is mostly on paclitaxel,” she states.

The step further is to compare each type of DCB (as there is no class effect) with the latest generation DES in de novo lesions in clinical trials sufficiently powered for a clinical primary endpoint. This is currently ongoing in the REVERSE trial for the B Braun paclitaxel coated balloon (large vessels ≥3mm),

TRANSFORM 2 with the Concept Medical sirolimus-eluting balloon (small vessels ≤3mm) and Selution DeNovo (a large DCB study in de novo lesions, any size of the vessel) for the Medalliance Sirolimus-eluting balloon.

Turning to the question of whether DCBs can be considered as moving into the “primetime” for PCI, Morice says that the signs are positive. “The rationale of the drug-coated balloon is that it is a new paradigm,” she comments. “It preserves the arterial physiology, allows positive remodelling of the vessel, avoids the metallic scaffold complications and allows short DAPT therapy in stable coronary artery disease patients.” bbraun.com/dcb bbraun.com/dcb

Contingent on positive trials comparing DCBs to stents in de novo lesions, the devices may play an “important role” in PCI procedures in years to come, she predicts, commenting that this change in perception is likely not to be far away when the results of the trials cited above will be available, if they have a positive outcome.

“We know all the success we have obtained with drug-eluting stents, but we also know that they have some limitations,” she adds. “DCBs may play a big role, complementary to drug-eluting stents, to treat our patients better according to the nature of the disease, the size of the artery, the location of the lesion, the quality of predilatation, or the grade of residual calcification. The more efficient and safer devices we have the better we can treat our patients.”

While new indications are explored through ongoing trials and further evidence mounts on the indications for which DCB are now seen as established therapy, there is likely to be a continuing growth in the interest in this device technology into the future. Hinging on the results of future research in de novo large vessels, DCB-usage could increase to 30–40% of cases, Morice speculates.

As the field evolves, emerging data will shape the future role of DCBs in PCI. Morice comments that the continuation of research into the utility of DCBs is among the most eagerly anticipated fields of research in coronary interventions currently underway. “For coronary disease this is the most exciting research that is going on. We now know that there are some limits of the DES, and, if DCBs work as expected, restoring the vessel with nothing left behind is a dream.”