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SAN DIEGO -- A polymer-free, drug-coated stent with short dual antiplatelet therapy (DAPT) was better than a bare-metal stent (BMS) benchmark for efficacy and safety, the LEADERS FREE II U.S. pivotal study showed.

For the primary safety endpoint of MI or cardiac death, the BioFreedom biolimus A9-coated stent met both noninferiority and superiority criteria against propensity-matched BMS patients from the prior European randomized trial, LEADERS FREE. The 12-month composite rates were 8.6% versus 12.3%, respectively (HR 0.67, 95% CI 0.51-0.88).

For the primary efficacy endpoint of target-lesion revascularization, the drug-coated stent again came out superior (6.1% vs 9.3%, HR 0.63, 95% CI 0.45-0.87), reported Mitchell Krucoff, MD, of the Duke Clinical Research Institute in Durham, North Carolina, at the Transcatheter Cardiovascular Therapeutics (TCT) conference.

Both MI and cardiac death, as well as urgent target-lesion revascularization, target-vessel revascularization, and any revascularization, significantly favored BioFreedom.

"These are patients who, by and large, have been excluded from every pivotal DES [drug-eluting stent] study and every pivotal DAPT study," Krucoff noted at a TCT press conference. "Whether the findings as we get more numbers could be more heterogeneous; whether this stent platform is unique or different than other state-of-the-art DES platforms; whether 30 days of DAPT versus 3 months versus 6 months -- there are a lot of unanswered questions here."

"But as an evidence-based reality in patients we treat all the time -- and in American practice, some centers are still putting bare-metal stents in double digits of PCIs [percutaneous coronary interventions] in their institutions -- I think bringing this stent forward with a label for 30 days [of DAPT] in HBR [high-bleeding risk] patients is a yes," he added.

The trial was designed to support approval by the FDA, although TCT press conference discussant David Cohen, MD of Saint Luke's Mid America Heart Institute in Kansas City, Missouri, noted that "it's unusual for the FDA to allow a single-arm study to register something in the United States."

But it's also rare that a prospective, double blind, well-powered, well-designed, pivotal randomized trial has already been done outside the U.S. to back up such findings, which is the case here with the original LEADER FREE data, Krucoff noted.

"You could say that what LEADERS FREE alerts us to is a safety signal that our intuitive behavior in clinical practice of putting bare-metal stents into patients, who we know are high-bleeding risk so we're only going to treat them with 30 days of DAPT, is actually a safety signal that we're doing potentially harm based on at least one study as available evidence," he said. "There's no question FDA decisions are primarily driven by safety concerns."

"I think if we had this stent available in the United States with this data, we would stop using bare-metal stents," suggested Cohen, who was on the steering committee for LEADERS FREE.

BioFreedom Vs DES

However, other data presented at the same session suggested there was no place for the stent outside the high-bleeding risk population.

In an all-comer population of 3,151 patients in the randomized SORT OUT IX trial, the BioFreedom stent with a 6- or 12-month DAPT regimen was noninferior to the biodegradable-polymer Orsiro stent for safety but wasn't for efficacy.

Target lesion revascularization at 12 months was 2.77-fold more common with BioFreedom than Orsiro (3.5% vs 1.3%, P<0.0001).

"We wanted to see if the BioFreedom stent was as good as a gold-standard drug-eluting stent, and I think we can say the efficacy is not as good," said Lisette Okkels Jensen, MD, PhD, of Odense University Hospital in Denmark, said at the press conference.

"I would not use it in patients unless there was a reason you need to lower the duration of DAPT," concluded Antonio Colombo, MD of the EMO GVM Centro Cuore Columbus in Milan.

Cohen agreed. "I think the single message from the two BioFreedom studies is if a bare-metal stent is what you were thinking of using, and you have a drug-coated stent, use that because it's safer and better," he stated. "But if you don't have it, like right now we still don't have that option, the right answer might turn out to be, in the long run, that the current drug-eluting stents are fine and better for those patients. But...we don't know the answer to yet."

The patient groups still getting BMS in U.S. practice are typically those who've recently had a bleed, those who urgently need surgery, and those who are on anticoagulation, for whom there's still a general lack of confidence in the studies suggesting shortening aspirin duration, Cohen noted.

What could obviate drug-coated stents are the studies underway with 30 days of DAPT for current generation DES in high-bleeding risk patients. "If those look good, maybe we get rid of all of these things and just go with good, old drug-eluting stents," Cohen suggested, although noting that these studies don't have true control arms.

"They do these studies to help sort things out, but sometimes they don't," Cohen concluded, laughing.

Polymer-Free, Short DAPT

Another study discussed at the press conference explored a novel amphilimus-coated stent, free of polymer, versus the latest generation of permanent-polymer, zotarolimus-eluting stents. The study was done in all-comers in a European population, with 30-day DAPT for the subset of troponin-negative patients.

The ReCre8 trial showed noninferiority for 12-month target lesion failure with the novel stent compared with DES (6.2% vs 5.6%, P=0.67). Net adverse clinical events at that point were 12.2% versus 11.6%.

However, the short DAPT subset of about 900 patients had too few events to really say much about safety and efficacy, cautioned Pieter Stella, MD, PhD, of University Medical Center Utrecht, the Netherlands.

The whole premise of getting rid of the polymer was to shorten DAPT regimens, Cohen noted. But only BioFreedom has U.S. data even in the works, so it would be, "if it gets approved, the only one for some time, I suspect," he noted.

"I think it's probably time to do a high bleeding-risk study with thin-strut drug-eluting stents to see if we can achieve efficacy and safety beyond what we're seeing with the BioFreedom," said press conference discussant Sunil Rao, MD, of Duke University Medical Center and Durham VA Medical Center in North Carolina.