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The modern field of percutaneous coronary intervention (PCI) has come to be dominated by drug-eluting stents (DES), but there are many instances in which “leaving nothing behind” in the vessel is an attractive prospect. Proponents of this approach, including Tuomas Rissanen (North Karelia Central Hospital, Joensuu, Finland), believe that using a drug-coated balloon (DCB) is an effective alternative to the stent that offers a range of benefits in selected patients.
Underpinning this belief is a wealth of clinical data, including from registry-based studies, and randomised trials that inform treatment in a wide set of clinical and anatomical scenarios. Among the leading devices in the field is the paclitaxel and iopromide-coated SeQuent® Please product family (B. Braun)—widely acknowledged as the best-investigated DCB in the market—which has clinical evidence from more than 110 published studies, totalling more than 25,000 patients, and stretching back almost 15 years since its entry into the market.
In this interview, Rissanen discusses the clinical indications that are most suited to the use of a DCB, the studies that have been most impactful to the field, and how having a proven device backed by a wide set of data is key.
“The fundamental difference to a stent is that no foreign body material is left in the artery that may cause later problems such as stent thrombosis,” Rissanen explains, discussing what separates PCI with a DCB to stent implantation. In simple terms, the DCB delivers an antirestenotic agent directly to the lesion, usually either paclitaxel or sirolimus mixed with an excipient helping to move the drug from the balloon catheter to the vessel wall.
“Stents are very useful when the treated vessel needs mechanical support due to collapse of the vessel or significant flow-limiting dissection—in fact, stents were developed for these two purposes,” comments Rissanen. “However, when the predilatation result is good and there are no problems that would need a metallic implant, then it is best just to use a drug coated balloon catheter delivering an antirestenotic drug,” he advises.
“An advanced interventional cardiologist should absolutely have both tools in the toolbox,” Rissanen comments, pointing out that the DCB and DES offer complementary characteristics.
Predominantly the DCB has been seen as a tool for treating in-stent restenosis, where it carries a class I recommendation with evidence type A in guidelines from the European Society of Cardiology (ESC) and European Association for Cardio-Thoracic Surgery (EACTS), based largely on studies performed with the SeQuent paclitaxel and iopromide coating, including the PACCOATH ISR I and II or PEPCAD trials. However, more recently there has been an increase in interest in the use of DCBs in de novo lesions, where the therapy has been shown to be safe and effective in numerous scenarios.
“Depending on the patient and lesion characteristics, and most importantly, on the result of the predilatation of the lesion, the method that is best for the patient should be chosen,” says Rissanen. Typically, an adequate vessel preparation involves achieving less than 30% stenosis, no flow-limiting dissection, and a fractional flow reserve (FFR) of >0.8.
Rissanen offers the view that this is particularly appealing among patients that are at high-risk of bleeding, as the DCB allows the clinician to stop antithrombotic medication within a month after the procedure in stable coronary artery disease patients, without an increase in event rates. Besides DCB-only usage in standard de novo lesions, he notes that there are also anatomic scenarios for DCB-only PCI, including, for example, in complex bifurcations, where the side branch, main branch, or both branches, can be treated using a DCB.
“The advantages of DCB-only therapy over stenting in this situation are that the side branches that are in the treatment area are not that easily occluded,” Rissanen adds. “Also, the lack of metallic implant allows later positive remodelling of the vessel and of course eliminates the risk of stent thrombosis.”
Additionally, in recent years this technology is gaining more traction in complex and diffuse coronary artery disease being used alongside stents to reduce the overall stent-burden.
Turning to the data supporting the use of DCB in coronary lesions, Rissanen identifies two studies—BASKET-SMALL-2 and DEBUT, both of which used SeQuent Please/NEO DCBs—as being the standout studies to have led the field. BASKET-SMALL-2, results of which were published in The Lancet in 2018, is an open-label randomised non-inferiority trial investigating the use of DCB in small vessels, comparing 758 patients with lesions <3mm in diameter receiving either a DCB or a DES. Results of the trial demonstrated the non-inferiority of the DCB versus DES, with major adverse cardiovascular events (MACE) shown to be comparable between the two groups (7.5% for the DCB group vs. 7.3% for the DES cohort). Rissanen notes that three-year follow-up from the trial, published in 2020, has shown consistent and durable results, while a sub-group analysis on high-bleeding-risk patients, in particular, has highlighted the benefit of DCB versus stenting.
In DEBUT, a single-blind, randomised, non-inferiority trial, examining the treatment of de novo coronary lesions in patients with high-bleeding risk using DCB or a bare metal stent, results, published in The Lancet in 2019, showed that the DCB was superior to the stent against a primary outcome of MACE at nine months. A total of 208 patients were enrolled in the trial, with MACE having occurred in one patient (1%) in the DCB group versus 15 (14%) in the stent group.
The accumulation of data continues and according to Rissanen, of the more recent studies to influence thinking on DCBs is the 2020 publication of a meta-analysis in the Journal of the American College of Cardiology (JACC), authored by Bruno Scheller (University of Saarland, Homburg/Saar, Germany) is fundamental. This took data from 26 randomised controlled trials, including 4,590 patients, looking at paclitaxel-coated devices, and reached the conclusion that the use of paclitaxel DCBs for treatment of coronary artery disease is safe in the long term.
Outside of these landmark trials, Rissanen also points to a wealth of further research that has shaped perceptions on DCB in diverse patient populations. Among them is PEPCAD-NSTEMI, a trial that addressed DCB-only therapy in non-ST-elevation myocardial infarction (NSTEMI) patients, finding that treatment of coronary de novo lesions with DCB was non-inferior to stenting with bare metal or drug-eluting stents. This was underlined in a sub-group analysis of the BASKET-SMALL 2 trial, where non-inferiority to DES in acute coronary syndrome (ACS) patients, including around half with NSTEMI, was shown. Rissanen also highlights the REVELATION study, addressing a DCB-only approach in STEMI using FFR measurement as a surrogate marker.
Do these data translate into clinical practice, and should it inform decision-making when it comes to device selection? Yes, according to Rissanen. “The SeQuent Please DCB has shown consistently good clinical results in many registry-based studies and randomised clinical trials,” he comments. “These trials involve different clinical and anatomical scenarios and cover also more complex situations such as bifurcations, calcified lesions and even chronic total occlusions (CTOs).
“SeQuent Please DCB currently has the most clinical data to show its safety and efficacy. This is important as the patient population in the cath lab nowadays is very complex. You can trust the device that you are using in these circumstances and convince also your patient that he or she is receiving the best available treatment.”
Summing up why he chooses only to use the devices that have the best available evidence, Rissanen concludes: “In our centre we use devices based on the proven clinical data. It is both cost-effective and best for the patient.”
Read more about coronary drug coated balloons here.