ReCre8: Physician-Led Study Shows Noninferiority of Polymer-Free Stent Compared With Permanent-Polymer ZES at 1 Year

SAN DIEGO, CA—A new, polymer-free, amphilimus-eluting stent is noninferior to a market-approved, permanent-polymer zotarolimus-eluting stent (ZES) with regard to target lesion failure (TLF) in an “all-comers” population at 12 months, according to the results of the ReCre8 trial.

Pieter R. Stella, MD, PhD (University Medical Center, Utrecht, the Netherlands), presented the results today during a late-breaking trial session at TCT 2018. The ultimate goal with these newer devices, he reminded the audience, has always been to reduce complications that were seen with early-generation DES—in particular, the risk of stent thrombosis believed to be associated with the polymers used to deliver the drug.

ReCre8, which was simultaneously published in Circulation, was an investigator-initiated trial that randomized 1,532 European patients to PCI with the polymer-free Cre8 stent (Alvimedica) or the Resolute Integrity ZES (Medtronic). Troponin-negative patients received 1 month of dual antiplatelet therapy (DAPT), while troponin-positive patients were put on DAPT for 12 months.

The trial showed the Cre8 stent was noninferior to the permanent polymer stent with regard to the endpoint of target lesion failure at 12 months (6.2% vs 5.6%; P = 0.0086 for noninferiority), with similar rates of net adverse clinical events at 12 months (12.2% vs 11.6%). These results were maintained throughout multiple subgroups.

In a substudy of patients treated with 1 month of DAPT (n = 892), the overall rate of stent thrombosis was 0.9%. TLF in this cohort was 6.8%, and there were no significant differences in safety outcomes between the two stents. A second substudy of 304 diabetic patients showed no differences between the Cre8 and permanent polymer stents with regard to TLF (7.3% vs 7.8%). Both of these subanalyses were not powered for outcomes, Stella warned.

Waiting for 3-Year Data

In a media briefing, David Cohen, MD (Saint Luke’s Mid America Heart Institute, Kansas City, MO), questioned whether the whole polymer-free hypothesis may be coming up empty-handed. “The whole promise with polymer-free DES is shortening the DAPT beyond what you can achieve with current durable polymer stents, but . . . we see here results that are very comparable,” he said. “[Is there] any reason to choose this stent when [DES] work just as well?”

Stella responded that the Cre8 stent has some features that make it a “pleasure” to work with, but said ultimately this question won’t be answered until 3-year data, which might illuminate more details about TLF outcomes, becomes available.

Antonio Colombo, MD (San Raffaele Hospital, Milan, Italy), suggested that maybe future trials of this nature be extended to at least 2 or 3 years of follow-up from the outset. Otherwise, “it’s a lot of effort to find almost nothing,” he commented.

Regardless, Sunil Rao, MD (Duke University Medical Center, Durham, NC), told TCTMD that “in a broad sense, more options for the treating physicians are a good thing.” In general, he added, trials like these “all use different noninferiority margins, and that concerns me a little bit because these are absolute differences they're looking at, whereas in the pharma world, we're used to looking at relative differences. So the noninferiority margins tend to be very tight in the pharma world, whereas on the device side, they tend to be broader. It's hard I think to necessarily use these trials to choose one stent over the other.”

Ultimately, these data add to the bigger picture that “we're starting to see a lot of similar outcomes across the stent platforms, which is going to further commoditize drug-eluting stents. Hopefully that will make the drug-eluting stents more affordable and bring the prices down,” Rao said. “There's a lot of downward pressure on prices already, and I think that's going to continue as we have more platforms available.

DAPT and Diabetics

Following Stella’s presentation of the results in the session, panelist Didier Carrié, MD, PhD (Hôpital Rangueil, Toulouse, France), dug deeper into the substudies, saying that he was “a little bit disappointed” in the results seen within the diabetic population.

“We need to keep in mind that this is an all-comers study and a big box of data, and we really still need to look into it,” Stella replied. “One of the explanations could be that results of the diabetic arm could have been negatively influenced by the short DAPT. We still don't know is short DAPT safe, yes or no? I think we need to be very careful of that.”

Panelist Robert Byrne, MBBCh, PhD (Deutsches Herzzentrum, Munich, Germany), added that “we need more compelling evidence before we can move to using 1-month dual antiplatelet therapy for troponin-negative patients. This and other studies showed the acceptable results aren't really enough, because we need this randomized comparison against 6 months.”

It does depend on the patient, however, said panelist Tullio Palmerini, MD (Policlinico S. Orsola, Bologna, Italy). “For example, in patients with complex multivessel coronary artery disease, even if they are stable patients and troponin negative, if you put in a long stent, multiple stents, or full metal jacket, it’s not advisable to give just 1-month DAPT,” he said. “This is consistent with the data of this trial, in which four out of eight stent thromboses were in complex patients treated with 1-month DAPT.”

“If you want to stop DAPT at 1 month in a patient with a simple lesion, it seems to be safe regarding stent thrombosis. TLF is something else,” Stella emphasized. “So, be very cautious.”