Drug-coated balloon-only angioplasty is recommended by evidence-based guidelines for the treatment of in-stent restenosis while there is also evidence to support their use in small-vessel disease and patients with high bleeding risk [5, 17, 18]. Following a recent meta-analysis though, concerns have been raised regarding the safety of paclitaxel devices for peripheral artery disease [12]. In SPARTAN DCB study, paclitaxel DCB was not associated with increased late mortality, up to 5 years of follow-up. Instead, there was a trend for better survival when compared with second-generation DES.
Our results are consistent with two recent meta-analyses. The recent DAEDALUS study in patients treated with DCB or DES for in-stent re-stenosis showed that there was no significant difference in late mortality associated with DCB. This conclusion is limited however, by the fact that follow-up was limited to 3 years and thus might have missed a true late effect [19]. In addition, it is difficult to draw definitive conclusions from that study for late mortality relating to paclitaxel, as this was a subgroup analysis and the patient groups were heterogeneous given the previous stent implantations including bare metal stents and paclitaxel DES. A most recent meta-analysis specifically investigating the mortality of paclitaxel DCB for coronary intervention did not show increased mortality with DCB [20]. However, this meta-analysis included significantly heterogeneous studies comparing paclitaxel DCB with control treatments such as plain old balloon angioplasty, bare metal stents, paclitaxel and non-paclitaxel drug-eluting stent mostly in the setting of in-stent restenosis.
In the SPARTAN DCB study, we included large numbers of patients treated for de novo coronary artery disease and ensured homogeneity of the groups by excluding patients with previous PCI or patients who received both DCB and DES either at their index or subsequent PCIs. As such, our groups of DCB and DES were well-matched for patient characteristics and angiographic findings. We have demonstrated that there is no evidence of increased late mortality associated with paclitaxel DCB compared to non-paclitaxel second-generation DES for de novo coronary artery disease up to 5 years of follow-up. In fact, there was actually a trend towards better survival with DCB, a finding consistent with the most recent meta-analysis [20]. Furthermore, we specifically investigated a late paclitaxel effect by analysing only patients who were alive at 2 years, with no evidence of increased late mortality associated with paclitaxel DCB either.
Following a meta-analysis raising concerns about a possible long-term mortality signal due to paclitaxel-eluting devices for peripheral vascular disease [12], an intense debate about the conclusion and various limitations of that study has been triggered in the literature [11, 21,22,23]. Whilst subsequent studies have failed to confirm these initial concerns, the FDA has nonetheless initiated an ongoing investigation for this matter [15]. Despite the similarities in peripheral and coronary DCB, there are also major differences. For example, the dose of paclitaxel in DCBs for coronary artery disease is about an order of magnitude lower compared to the dose of paclitaxel in paclitaxel-coated devices for peripheral artery disease [16] making it therefore unclear whether, even if the results of the DCB for peripheral vascular disease were adverse, how this would translate to the coronary DCB PCI. Furthermore, the underlying mechanism leading to a possible increased late-mortality signal with DCB for peripheral artery disease remains to be defined. Nevertheless, given that the outcomes that were notably concerning included cardiovascular mortality, it is crucial to study the results of paclitaxel DCB for coronary artery disease carefully and provide assurance of safety.