This advertorial is sponsored by Sinomed
As newer-generation drug-eluting stent (DES) technologies continue to raise the bar for the treatment of coronary artery disease (CAD), offering improved rates of target lesion failure (TLF), low levels of stent thrombosis, and benefits in revascularisation compared to earlier-generation devices, the search for the next frontier in DES innovation becomes ever more challenging for device manufacturers.
A new entrant into this arena is the HT Supreme (Sinomed), a “healing targeted”, biodegradable polymer coated, sirolimus-eluting stent. While contemporary DES platforms have emphasised delayed healing through prolonged drug delivery, with the aim of suppressing the body’s response to the barotrauma injury of implanting a thrombogenic foreign body, HT Supreme is based upon the “wound-healing window” concept. This focuses on facilitating early healing and restoring natural endothelial function soon after stent implantation, and could benefit patients when used with a shorter duration of dual antiplatelet therapy (DAPT).
“The concept was to develop a drug-eluting stent with a known drug [sirolimus] that could be eluted with a pharmacokinetic profile that would maximise its ability to supress neointimal hypoplasia, while promoting early endothelialisation,” explains Martin B Leon, (Columbia University, New York, USA), who is the chairman of the Executive Committee for the PIONEER III study—the largest randomised trial to date to evaluate the use of the HT Supreme device.
Leon explains that the HT Supreme stent releases at least 80% of its drug within the first month of implantation, a process that takes place simultaneously alongside degradation of the biodegradable polymer coating. This leaves behind an electrografted thromboresistant base layer that is designed to promote rapid endothelial coverage and accelerate a positive healing response, as well as protecting the underlying metal stent from corrosion and heavy metal ion release. “That positive healing response is the greatest protection against platelet deposition, thrombus formation [and] blood clots forming on the device, which can cause late safety concerns,” says Leon.
“You could look at it as a super bare metal stent, because it has got a smooth permanent layer on it,” comments Andreas Baumbach (Queen Mary University of London, London, UK), who also participated as European co-principal investigator in the PIONEER III study.
According to Baumbach, after completion of drug delivery and once the biodegradable polymer has fully degraded, what remains is a stent that “really encourages healing”. He comments: “In order to have good long-term results, you need to have a vessel that is able to restore function.”
Patrick Serruys (National University of Ireland, Galway, Ireland), who chaired the CE mark trial PIONEER I, agrees that the promotion of endothelial function is one of the important facets of this technology and comments that it offers the potential for clinical benefit in CAD patients in the long term.
“A good endothelium is less permeable for a lot of molecules, including LDL cholesterol,” he says. “We believe that because the endothelium is there early, and is of good quality, there will potentially be less thrombogenic and atherosclerotic problems in the long term, but that is something that has to be proved.”
Promoting endothelial function
To date, study of the HT Supreme stent has focused on the non-inferiority of the device in terms of safety and efficacy to two best-in-class, durable polymer everolimus-eluting stents, for the treatment of CAD—Xience (Abbott) and Promus (Boston Scientific). PIONEER III was carried out in 74 participating centres in North America, Europe and Japan, enrolling 1,629 patients (randomised 2:1) with a primary composite endpoint of TLF at one year. The first 12-month results from the study, presented at the American Heart Association 2020 scientific sessions (AHA 2020, 13–17 November, virtual), showed that the HT Supreme met the non-inferiority TLF endpoint at 5.4% compared to 5.1% from the durable polymer DES (p=0.002). A grouped analysis of secondary endpoints also showed a numerically-better result for HT Supreme in cardiac death or target-vessel myocardial infarction (TVMI) with 3.5% in the HT Supreme arm compared to 4.6% in the control arm (p=0.27). Lower late stent thrombosis data (HT Supreme 0.1% compared to DP DES 0.4%, p=0.22) also suggested exceptional safety for the HT DES.
Commenting on these results, Leon says: “Certainly the results indicate that the major endpoints, TLF and clinically-driven target lesion revascularisation were low and equivalent to the comparator stents—which is encouraging.”
Furthermore, he adds that there were no major differences in stent thrombosis, but a trend towards benefit from the standpoint of a composite safety endpoint, comprising TVMI, stent thrombosis, and cardiovascular death.
However, Leon also points out that while PIONEER III shows “trends going in the right direction”, longer-term follow-up will give a clearer picture of whether the wound-healing concept brings about real clinical benefit. “If this device is going to truly live up to its technology reputation, then it should reveal itself not in the first year, but in the several years thereafter in terms of safety—specifically in late stent thrombosis and target-vessel myocardial infarction,” he comments.
Further data on the performance of the device is anticipated, with Baumbach having presented a subgroup analysis of the performance in complex lesion anatomy from the PIONEER III study at EuroPCR (18–20 May, virtual), as well as further ongoing landmark analyses in the pipeline up to five years. Alongside these studies, the PIONEER IV trial is also underway—a prospective, single-blind, 1:1 randomised controlled multicentre study in an all-comer population prescribed only one month of DAPT—comparing outcomes between angiography-derived physiology guidance and standard guidance, with unrestricted use of HT Supreme. The trial has a patient-oriented composite endpoint of all-cause death, stroke, myocardial infarction, and revascularisation, which will be assessed at one year, while patients will be followed for up to three years.
Baumbach says PIONEER IV is an “exciting trial” that will answer questions around the use of HT Supreme, as well as having wider implications for the practice of percutaneous coronary intervention (PCI), including comparing quantitative flow ratio (QFR) and fractional flow reserve (FFR) measurements. The study of a one-month course of DAPT will be an important aspect of the trial, offering insights into the scope to reduce bleeding events, particularly in patients considered at high risk of bleeding, who may not have been considered for stents in the past.
For Serruys, chairman of the study, these are important aspects of the PIONEER IV trial, which will offer greater insight into the applications of the HT Supreme, and answer questions for the future of cath lab practice. Treatment of “physiologically significant” lesions is an aspect of interventional cardiology that is at the heart of the study. Serruys adds: “There has been an excess of stenting—and the more metal you put in the coronary artery the worse it can become.” This is where the trial’s use of QFR will play a central role—which Serruys says will “justify” the treatment offered to patients taking part in the trial.