'Healing' Stent on Par With Durable Polymer Stents: PIONEER III

Patrice Wendling

November 24, 2020

A novel stent designed to target early wound healing met the primary noninferiority end point at 1 year in the PIONEER III trial, but differentiating itself from current high-performing durable-polymer drug-eluting stents (DES) will require more.

The Supreme HT (healing-targeted) DES (Sinomed) works to restore endothelial function after implantation via two mechanisms, according to Alexandra Lansky, MD, Yale School of Medicine, New Haven, Connecticut.

The investigational device combines rapid sirolimus delivery (90% elution by 28 days) and polymer degradation (~4 to 6 weeks) with a permanent, electro-grafted base layer that promotes endothelial cell migration and healing and protects the underlying metal stent from chronic corrosion and ion leaching, she said.

The global trial was designed to support regulatory approvals in the United States and Japan and randomized 1632 patients with acute and chronic coronary syndromes to the HT-DES or either a Xience (Abbott) or Promus (Boston Scientific) durable-polymer DES. Patients could have up to three de novo native lesions in up to two major vessels but not an ST-segment MI or chronic total occlusion.

At 12 months, the primary end point of target-lesion failure (cardiac death, target vessel myocardial infarction [MI], or ischemia-driven target lesion revascularization [TLR]) occurred in 5.4% of HT-DES patients and 5.1% of standard DES patients. This met the study's noninferiority margin of 3.58% intended to preserve 60% of the treatment effect of DES vs bare metal stents.

Rates of cardiac death (0.3% vs 0.8%; = .18) and target-vessel MI (3.4% vs 4.1%; P = .45) trended lower with the HT-DES, but ischemia-driven TLR rates were twice as high (2.3% vs 1.0%; P = .06).

There were no overall differences in stent thrombosis, although late stent thrombosis favored the HT-DES over the standard DES (0.1% vs 0.4%; P = .22).

"Whether these early safety measures translate into significant clinical benefit in the longer-term will be assessed at 5-year follow-up," Lansky said when presenting the results at the recent virtual American Heart Association Scientific Sessions.

Discussant Alexandre Abizaid, MD, PhD, Instituto Dante Pazzanese de Cardiologia, São Paulo, Brazil, said, "this technology has a great rationale to potentially impact the safety profile," but questioned whether it will show superiority against current DES, which have humbled even fully absorbable scaffolds. "A 1% TLR is hard to beat," he said.

"When I see a platform like this, my first reaction, and perhaps the sex appeal of this new device, is to prescribe short DAPT [dual-antiplatelet therapy]," he added. "Is there anything in the planning that you are designing or do you think that, just with the rationale and previous studies, we can prescribe short DAPT in this new platform?"

Lanksy said the latter would be premature until long-term follow-up results are available, but "if the theory holds out and we show that we have superior outcomes and a safe platform, that is absolutely the next step. There have been many conversations and discussions about shortening DAPT with this technology."

Session comoderator Wayne Batchelor, MD, MHS, Inova Heart & Vascular Institute, Falls Church, Virginia, said the prespecified landmark analysis will be important because events will start accumulating over time, but noted that the noninferiority margin was "fairly liberal" and based on a willingness to accept up to 60% efficacy relative to the gold standard DES stents.

"How do we move the ball further? Are we stuck just saying all stents are equal, or are we going to be able to get to the point where we can really show that a healing stent is superior?" he asked.

Lansky retorted, "it's a little bit of a loaded question," observing that current DES technologies certainly achieve very good results but that newer stents like the Orsiro have been shown to be superior to Xience at 1 year.

"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 that we want to try and pursue and try and improve over time," she said. At a minimum, a signal of benefit during follow-up would suggest the need for larger trials or perhaps that DAPT could be reduced.

"We've come a long way on the basis of some very important landmark clinical studies and at least I'm not entirely ready to say this is as good as it gets," Lansky said.

Asked in which patients the Supreme HT would be indicated, if approved, or whether it's a workhorse stent, Lansky said the results can't be generalized to ST-segment MI and chronic total occlusions, but "are outstanding considering this is being tested against the tried-and-true Xience. So I would say this is behaving like a workhorse stent based on the results we are seeing and could be used in the vast majority of patients, for sure."

Róisín Colleran, MB BCh, Mater Private Hospital, Dublin, Ireland, however, struggled with a 3.5% noninferiority margin that was "quite wide" and a TLR rate for the Supreme HT that was more than twofold higher with a trend toward statistical significance.

"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're happy to accept as noninferior," she said.

Lansky said the higher TLR rate was "numerically true," but that the study was not powered to detect meaningful differences when event rates are so extremely low. Follow-up was also complicated by the COVID-19 pandemic.

"So I would use a lot of caution when you read into those types of differences or trends to think that they are meaningful," she said. "I doubt that they are, and I don't think the statistics would bear that out."

Colleran responded: "I guess the low rate in the control arm might indicate a lower-risk patient cohort in the overall trial. But it would be interesting to see with larger numbers powered to show differences with respect to these endpoints."

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, and Veryan Medical; and serving as a speaker or receiving consulting fees from Sinomed, Astra Zeneca, Abiomed, Microport, and Trireme. Abizaid reports serving as a speaker for Boston Scientific. Batchelor reports relationships with Medtronic, VWave, Idorsia, and Boston Scientific; and receiving research support from Abbott Medical. Colleran reports having no relevant conflicts of interest.

American Heart Association (AHA) Scientific Sessions 2020: Abstract LBS.05. Presented November 15, 2020.

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