The use of polymers to modulate the drug release from drug-eluting stents (DES) has undergone several major changes over time. Thirteen years ago, the ELUTES trial first suggested that paclitaxel-coated stents might reduce restenosis without requiring a polymer , but further evaluations of similar devices were not conclusive . Based on these findings, the first-generation permanent polymer-coated DES thus became the gold standard . Over time, however, late thrombotic complications became apparent and were largely attributed to the polymer coatings . Prolonged or indefinite dual antiplatelet therapy (DAPT) was then considered necessary by many until improved permanent polymers and biodegradable polymers were shown to be safer and allowed the pendulum to slowly begin to swing toward less-aggressive antithrombotic regimens. More recently, thanks to better drugs and improved platforms , polymer-free stents are making a comeback, together with the potential for much shorter courses of DAPT. Indeed, in 2015, the LF trial documented that, with only 1 month of DAPT, the BioFreedom drug-coated stent (DCS) (Biosensors Europe, Morges, Switzerland) was both safer and more effective than a BMS in patients considered at high bleeding risk (HBR) .

In this issue, Waksman et al. report on an important and interesting first US experience with the polymer-free BioFreedom stent together with a short 3-month course of DAPT for 72 percutaneous coronary intervention (PCI) candidates presenting with stable coronary artery disease (CAD) . The main finding is a confirmation that the BioFreedom DCS has good efficacy in terms of angiographic late loss. It is also encouraging to note that there were no ST events despite reducing the DAPT course by 75% compared to the 12-month US guideline-recommended duration. Of note, 83% of patients were off DAPT at 4 months, suggesting good compliance with the protocol-mandated short antithrombotic regimen. HBR patients were largely excluded from the series, however, and that must explain the lack of any reported bleeding events, in stark contrast to the 1-year major bleeding rate of 7.2% for HBR patients observed in LEADERS FREE .

Although the observed late loss of 0.32 + 0.53 mm was lower than that of the chosen comparator, the trial was negative in terms of its primary end point and did not reach the predefined target of 0.21 mm for the DCS mean LL. However, as the authors point out, while the observed late loss is somewhat higher than that associated with most current polymer-coated DES, it may not necessarily be of clinical significance, and this view is supported by a target lesion revascularization (TLR) rate of only 1.5% at 9 months.

The fact that the median in-stent late loss is significantly lower at 0.19 mm than the mean value suggests that the late loss distribution is not Gaussian. Considering the cumulative frequency curves in Fig. 1 , it is apparent that while about 90% of lesions develop very little in-stent obstruction, there seems to be a minority of poor responders. If this finding were replicated in larger series with angiographic follow-up, it would of course be important to look for predictors of this apparent dampened response. Using median rather than mean late loss values, because they are better suited to very skewed datasets, the three currently available series are very comparable with a late loss of 0.17 mm [0.9, 0.39] for the 31 patients analyzed in FIM , 0.14 [0.06, 0.26] for the 100 patients in the EGO BioFreedom trial and 0.19 for the 66 patients in the current series by Waksman et al .

Excessive strut thickness has been shown to be responsible for an increase in restenosis rates after implantation of bare metal stents . It may be that the current version of the BioFreedom is less than ideal in that respect, since it is made of stainless steel with a strut thickness of 120 microns. A new cobalt chrome platform for the BioFreedom DCS is being developed, with struts of 81 microns, and should constitute a further improvement.

Interest in polymer-free stents is now on the rise with several innovative approaches: A hollow cobalt-tantalum drug-filled stent (DFS) allows for sirolimus to be released through laser-drilled holes without requiring any polymer , and the latest iteration of a polymer-free stent coated with a combination of probucol and sirolimus is currently being tested with short DAPT regimens [NCT02609698 and NCT02601157], as is a reservoir stent releasing amphilimus [NCT02328898] . The polymer-free future is bright again!