Bernardo Cortese (Fondazione Ricerca e Innovazione Cardiovascolare, Lodi, Italy and DCB Academy) has been among the leaders in research on the use of drug-coated balloons (DCBs) in percutaneous coronary intervention (PCI) across Europe. As the approach continues to gain ground among physicians, new devices using novel coatings such as sirolimus as an alternative to the current standard of care, paclitaxel, have begun to enter the market. Here, Cortese considers the important issues to consider when evaluating these two drugs.
Paclitaxel-coated balloons have been available in Europe since 2007 when the PACCOCATH study came out and since then many technologies with good outcomes have emerged. Sirolimus has taken quite a bit longer, with the first device marketed in 2016—Magic Touch (Concept Medical). From one point of view, sirolimus is more appealing to physicians as limus has won the war against paclitaxel in stents, and those who have come to DCBs relatively recently may hold this view. And, while sirolimus is bringing an important novelty to the field, we have seen a lot of data that paclitaxel works very well.
The drugs are truly different. As paclitaxel stays in the vessel wall for weeks and in some cases months, it can exert some cytotoxic effects in the case of over-dosage. At TCT 2023 (23–26 October, San Francisco, USA) Aloke Finn (University of Maryland School of Medicine, Baltimore, USA) presented data from a study comparing paclitaxel and sirolimus DCBs, showing that the latter was very keen to the vessel wall without any sign of toxicity, whereas the former was associated with some sort of toxicity. We do not understand if this is good or not, but we do know that in 60–70% of cases paclitaxel exerts late lumen enlargement.
When we started to test sirolimus with the Magic Touch DCB in Europe we decided to follow two different strands. One is to compare sirolimus to paclitaxel in a mechanistic study—TRANSFORM I—as well as in clinical studies in a broad population in comparison to stents (TRANSFORM II trial, ongoing). TRANSFORM I compared Magic Touch to Sequent Please (B Braun), which is a well-studied, well-performing paclitaxel-coated balloon. Magic Touch was just outside of the margin for non-inferiority as regards to the angiographic performance of the two devices, and we have speculated a lot about why this may be, with some important items to underline.
As a co-chairman of the study, I admit there are some drawbacks, including that we observed a consistent difference among the centres in terms of angiographic outcomes. We had some difficulty in enrolling patients, in part because of COVID-19, and so we had to lower the threshold of the quality of the centres in terms of their experience with DCB angioplasty. In one centre where paclitaxel worked much better, we observed that the lesion complexity was much higher. In another centre where Magic Touch performed better the lesions were much simpler. TRANSFORM I has provided important data to the field, and I believe it shows that in terms of angiographic performance, paclitaxel will always win over sirolimus.
One hypothesis that I would like to investigate, and is now being examined in PICCOLETO VI, is whether paclitaxel is better in penetrating into the vessel wall even if you have not achieved perfect lesion preparation. My hypothesis is that in complex lesions, sirolimus is not able to enter the vessel wall if you have not prepared the lesion perfectly. PICCOLETO VI is collecting data from the Sequent Please, Sequent Sirolimus (B Braun), Elutax (AR Baltic Medical), Selution (MedAlliance), Magic Touch, Prevail (Medtronic) and Pantera Lux (Biotronik) devices. We are studying not only angiographic performance at six months, but also physiology, and we have some interim analysis showing very interesting information from this study. The study has been sent for consideration as a presentation at EuroPCR 2024 (14–17 May, Paris, France) as a late-breaking clinical trial.
The second line of investigation, starting back in 2018, was EASTBOURNE, an investigator-driven prospective study with more than 2,100 patients. The 12-month follow-up, published in JACC: Cardiovascular Interventions in 2023, shows the safety and efficacy of the Magic Touch device in a broad population of coronary artery disease patients including small vessel disease and in-stent restenosis. We presented the two-year follow-up at EuroPCR 2023 (16–19 May, Paris France) and it is currently under review for publication, and we hope to have the three-year follow-up available this year. Interestingly we are doing a lot of sub-analyses, and have just published the Bifurcation and acute/stable coronary syndromes sub-analysis. The study of single antiplatelet therapy (SAPT) with DCB, as well as the performance in diabetic patients have been submitted.
We are gaining a good amount of angiographic data comparing sirolimus and paclitaxel DCBs, and I think that now we should compare the devices with good clinical backgrounds to drug-eluting stents. Physicians are using too many stents, so it is important that the comparator arm should be a stent, and this is one of the purposes of TRANSFORM II, another investigator-driven study. In this trial, we are randomising patients to Magic Touch versus any everolimus-eluting stent in de novo lesions. Now, we want to see with a clinical endpoint, if there is non-inferiority in the primary endpoint of target lesion failure (TLF), and also subsequent superiority in terms of net adverse clinical events (NACE), because we are reducing the duration of dual antiplatelet therapy (DAPT) with the sirolimus-coated balloon. So far we have enrolled over 660 patients and we are aiming for 1,825, and we hope to finish enrolment within one year.
I think that the future is bright for DCBs, at least in terms of preparing and creating a good programme of clinical trials. The outcomes we do not know, but we need to run these studies before we know the answer. So far, some well-studied paclitaxel DCBs should be used in the majority of patients, with sirolimus DCBs increasing their role in the arena.
