BIO-RESORT: Drug-Eluting Stents, With or Without Disappearing Polymers, Similar for Outcomes

Neil Osterweil

October 31, 2016

WASHINGTON, DC – Are coronary drug-eluting stents (DES) getting so effective as a technology that they have only so much more room for improvement?

A comparison of two very-thin-strut DES with different biodegradable polymers with a thin-strut durable-polymer DES[1] showed very low rates of an efficacy-safety composite end point at the 1-year follow-up: about 5% for each of the durable-polymer zotarolimus-eluting Resolute Integrity stent (Medtronic), the biodegradable everolimus-eluting Synergy stent (Boston Scientific), and the sirolimus-eluting Orsiro stent (Biotronik).

The results in each trial arm of the BIO-RESORT (TWENTE III) trial were so good that they tended to weaken the overall power of the study, acknowledged Dr Clemens von Birgelen (Thoraxcentrum Twente, Enschede, the Netherlands) presenting the trial at TCT 2016. The session moderator and invited discussants made the same observation.

Dr Clemens von Birgelen

"Recently, other DES trials also found lower-than-expected event rates, which actually may be more representative of outcomes of current PCI procedures, as opposed to when the study was designed," von Birgelen said.

The uniformly good results seen in the trial, which were published online in the Lancet, with von Birgelen as first author,may be attributable to recent improvements in PCI equipment, higher use of very potent P2Y12 inhibitors (48% of patients in the study were on dual antiplatelet therapy [DAPT]), higher use of radial vs femoral access, more PCI guidance by fractional-flow-reserve assessment, and a high proportion of patients with ACS, who have a lower probability of developing a periprocedural MI, he said.

The results "really make you feel good about PCI these days," commented Dr Paul S Teirstein (Scripps Clinic, La Jolla, CA).

"These outcomes are amazingly beautiful," Teirstein said, adding that "there's still room for improvement, but it's going to get harder and harder and we're not going to be able to get that much closer to zero." Teirstein spoke at press briefing prior to formal presentation of the trial.

Dr Stuart Spencer, executive editor of the Lancet, one of the invited discussants, agreed that "the success rate of PCI is so high that it's very, very difficult to find differences between stents, procedures, and so on."

He proposed that 5-year outcomes data will likely be needed before significant differences, if any, can emerge.

Four Centers in the Netherlands

In BIO-RESORT, investigators at four clinical centers in the Netherlands enrolled a total of 3154 patients who were sent to PCI with a DES according to guidelines. Of this group, 2448 (78%) had ACS, including 1073 with ST-elevation MI (STEMI).

The patients were randomly assigned to receive either one of the very-thin-strut biodegradable-polymer stents or the durable-polymer stent. The biodegradable-polymer stents differed significantly from one another in their composition (platinum-chromium for the Synergy stent and cobalt chromium for the Orsiro device) and in the type, distribution, and resorption speed (4 months with the Synergy DES, and 15 to 18 months with the Orsiro device) of their respective coatings, the investigators pointed out.

Exclusion criteria included planned surgery requiring interruption of DAPT within the first 6 months or patients who were judged to be potentially poorly adherent to follow-up procedures.

Primary Outcome

As von Birgelen reported at the sessions, 5.4% of patients on the durable polymer device and 4.7% of patients on each of the biodegradable very-thin-strut devices met the primary end point of a composite of safety (cardiac death or targeted vessel–related MI) and efficacy (target vessel revascularization) at 12 months. The results confirmed the noninferiority of each of the newcomers (P for noninferiority <0.0001), he said.

There were no statistically significant differences at 1-year follow-up between stent groups in any of the individual components of the composite end point or in clinically indicated target vessel revascularization.

DAPT use was high at all time points, with 97.3% of patients on therapy at discharge, 87.6% remaining on therapy at 6 months, and 85.6% still on it at 1 year. This enviable level of adherence can be attributed to the standard of care in the Netherlands, where patients have one general physician, one pharmacist, "and when we prescribe drugs for a year, they get it for a year," von Birgelen said.

There were four cases of definite stent thrombosis in 1172 patients who received the everolimus-eluting stent, four in 1169 patients assigned to the sirolimus-eluting stent, and three among patients assigned to zotarolimus-eluting stents; none of the differences were significant.

Longer Follow-up to Find Any Difference?

Although the 12-month follow-up data show similar results for all three styles of stent, considerably more follow-up will be needed to tease out important differences, commented Dr Dean J Kereiakes (Christ Hospital Heart and Vascular Center, Cincinnati, OH).

"The hypothesis that the distribution and time course for resorption of polymer may alter late clinical outcomes has not been resolved," he said at the briefing in response to a question from heartwire from Medscape.

"This is too early to determine whether polymer durability, distribution, and even time to drug elution can materially impact very late clinical outcomes."

Kereiakes expressed the opinion that in the long run, biodegradable polymer DES will be shown to have incremental benefits over durable polymer DES.

Echoing the comments of others, Dr Gregg W Stone (New York-Presbyterian Hospital/Columbia University Medical Center, NY), who moderated the session in which the data were presented, said that "as in many studies, event rates are lower than expected, which reduces the power of the study to show differences."

He added that the investigators used a one-side, 0.025-noninferiority margin that was split equally between the two biodegradable DES arms, "and some people would say that's only half the power you should have on that basis."

The BIO-RESORT trial was funded by research grants from Biotronik, Boston Scientific, and Medtronic. von Birgelen disclosed institutional research grants from those companies and from AstraZeneca. Teirstein disclosed consultant fees, honoraria, and speaker's bureau participation with Boston Scientific and Medtronic. The coauthors had no relevant financial relationships. Stone disclosed multiple relationships with other companies. Kereiakes disclosed a financial interest or arrangement with Boston Scientific and other companies. Spencer reported he had no relevant financial relationships.

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