‘Healing’ Stent Noninferior to Permanent-Polymer Device: PIONEER III
Demonstrating superiority against approved devices remains a challenge when only longer-term follow-up could reveal an edge.
The latest novel stent technology to square off against the industry standard has met the bar set by the PIONEER III trial for noninferiority, but whether the new device—this one with a “supreme healing” coating—yields any advantages will take time.
Alexandra Lansky, MD (Yale School of Medicine, Connecticut, CT), presented results of PIONEER III, testing the Supreme “healing-targeted” (HT) drug-eluting stent (Sinomed) earlier this week at the virtual American Heart Association 2020 Scientific Sessions.
According to Lansky, the HT-DES actively helps restore endothelial function after stent delivery using a combination of rapid sirolimus delivery (90% within 28 days) and polymer degradation (4 to 6 weeks), plus a base layer that promotes endothelial migration and protects the underlying thin-strut (80 µg) metal frame from chronic corrosion and ion leaching.
PIONEER III randomized 1,632 all-comer patients 2:1 to the HT-DES or to a Xience/Promus durable-polymer DES (Abbott and Boston Scientific, respectively); STEMI patients were excluded. Sites in the US, Canada, Europe, and Japan participated in the study, but 50% of patients were in North America, as required of a US Food and Drug Administration investigational device exception pivotal trial.
At 12 months, TLF (cardiac death, target-vessel MI, ischemia-driven TLR) had occurred in 5.4% of the HT-DES patients and 5.1% of the durable-polymer DES patients, a nonsignificant difference that met the trial criteria for noninferiority. The secondary endpoint of target-vessel MI was not significantly different between groups although it trended lower for the HT-DES (3.4% vs 4.1%; P = 0.45), as did the rate of cardiovascular death (0.3% vs 0.8%; P = 0.18). Ischemia-driven TLR, on the other hand, was numerically doubled in the Supreme group at 2.3% compared with 1% for Xience/Promus (P = 0.06).
Commenting on the latter difference during the discussion that followed Lansky’s late-breaking presentation, Róisín Colleran, MB BCh (Mater Private Hospital, Dublin, Ireland), pointed out that the noninferiority margin selected in PIONEER III was “quite wide,” and “we really do have to be careful how we define noninferiority.” In particular, the difference in TLR rates gave her pause, she said: “For me, this isn’t a stent that I’d be happy to use as an alternative to Promus or Xience, so it really does depend on our definitions and what we’d be willing to accept as noninferior.”
Lansky, however, called the TLR difference “numerically true” but stressed that the trial was not powered for this endpoint. Moreover, follow-up in the study to date has been complicated by the COVID-19 pandemic, which might in part explain the very low rate of TLR in both arms. “I would use a lot of caution when you read into those types of differences or trends to think that they are meaningful,” she countered. “I doubt that they are, and I don’t think the statistics would bear that out.”
Rates of late stent thrombosis, which also were exceedingly low, went in the opposite direction: 0.1% for the healing stent and 0.4% for the durable polymer device (P = 0.22). “Whether these early safety measures translate into significant clinical benefit in the longer term will be assessed at 5 years follow-up,” Lansky concluded.
I am not entirely ready to say this is as good as it gets. Alexandra Lansky
To TCTMD, Lansky observed in an email: “We are expecting that based on its unique design features, emphasizing early restoration of endothelial function, that the HT-DES will demonstrate safety benefit in the longer term and will be tested in a landmark analysis between 1-5 years.”
But she also acknowledged that new stent technologies represent a crowded field where devices—particularly those with bioresorbable polymers—have struggled to surpass the performance of approved permanent-polymer devices. “This bioresorbable-polymer DES, more than others, stands to demonstrate long-term safety benefit, because it is designed on a foundation of vascular biology emphasizing early restoration of endothelial function,” she told TCTMD.
Lansky was pressed on the same point following her presentation by moderator Wayne Batchelor, MD (Inova Heart & Vascular Institute, Falls Church, VA), who asked provocatively if maybe at this point “all stents are equal.” Discussant Alexandre Abizaid, MD, PhD (Instituto Dante Pazzanese de Cardiologia, São Paulo, Brazil), hammered the same point. “I love this new concept of polymer-free and a prohealing surface, [but] I think it’s going to be very hard to beat the current technology,” he said.
Lansky pushed back: “I think it depends on whether we want to accept the outcomes as they are now or if we want to improve on those outcomes. My perspective is that as we look at continued accrual of events that happen at the target site, at the intervened site, at a rate of 3% on an annual basis, I do think that is something we want to try and pursue.”
PIONEER III is designed and powered to look at this at 5 years, she added. Even a signal of benefit would suggest that this might be a stent that could be used with shorter durations of dual antiplatelet therapy, for example, in patients at high bleeding risk and thus would warrant additional studies. Her prediction, however, is that this could be a “workhorse stent,” useful in the range of acute and chronic coronary syndromes patients studied in this trial.
“We’ve come a long way on the basis of some very important landmark clinical studies,” she said. “And I am not entirely ready to say this is as good as it gets.”
Lansky A. Novel healing-targeted DES with synchronized antiproliferative drug delivery to target smooth muscle cell proliferation after DES implantation in coronary artery disease. Primary results of the PIONEER III Trial. Presented at AHA 2020. November 15, 2020.
- Lansky reports grant/research support from AstraZeneca, Abiomed, Abbott Vascular, Bard, Boston Scientific, Biocardia, Biotronik, Cagent, Conformal, Gore, Intact Vascular, KeyStone Heart, Lifetech, Limflow, Medinol, Micell, Microport, Myocardia, Reva, Shockwave Medical, Surmodics, Trireme, Venus, Veryan Medical; and speaker/consultation fees from Sinomed, AstraZeneca, Abiomed, Microport, and Trireme.
- Colleran reports no relevant conflicts of interest.
- Batchelor reports being a consultant to Medtronic, Boston Scientific, Abbott, VWave, and Idorsia, as well as receiving research support from Abbott and Boston Scientific.
- Abizaid reports serving on the speaker’s bureau for Boston Scientific.