3-Year BIORESORT: TLR Rate Lower With Ultrathin Sirolimus Stent

Neil Osterweil

May 21, 2019

PARIS — Small but significant differences in clinical outcomes with drug-eluting stents (DES) in small coronary vessels are beginning to emerge with longer follow-up in the BIO-RESORT trial.

As previously reported by theheart.org | Medscape Cardiology, the trial, comparing two very-thin-strut DES with different biodegradable polymers with a thin-strut durable-polymer DES, showed very low and similar 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).

But 3 years on, the curves charting target lesion revascularization (TLR) with stents implanted in small vessels — defined as angiographic reference vessel diameter below 2.5 mm — are starting to diverge, with rates of 2.1% for the sirolimus-eluting device, 4.0% for the everolimus-eluting stent, and 5.3% for the zotarolimus-eluting device, reported lead author Clemens von Birgelen, MD, PhD, Thoraxcentrum Twente, Enschede, the Netherlands.

Results of this prespecified analysis of BIO-RESORT were presented here at the Congress of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR) 2019 and simultaneously published online in JAMA Cardiology.

Still, TLR was only one component of the primary end point of target lesion failure (TLF), a composite of cardiac death, target-vessel-related myocardial infarction, and TLR. There were no differences in TLF among the stents at 3 years in this subanalysis.

The difference in TLR rates between the Osiro and Resolute Integrity devices was statistically significant, but the hazard ratio (HR) between the Osiro and Synergy stent was not significant.

"We performed also a multivariate analysis that confirmed that the Osiro stent was an independent predictor of a lower target lesion revascularization rate," von Birgelen said at press briefing prior to his presentation of the data in an oral session.

There were no significant between-stent differences in cardiac death, target vessel myocardial infarction (MI), or stent thrombosis.

BIO-RESORT Refresher

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

The patients were randomly assigned to receive one of the two 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 Osiro device) of their respective coatings, the investigators point out.

Exclusion criteria included planned surgery requiring interruption of dual antiplatelet therapy (DAPT) within the first 6 months and predicted poor adherence to follow-up procedures.

As previously reported, 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 and target-vessel-related MI) and efficacy (target vessel revascularization) at 12 months. The results confirmed the noninferiority of each of the newcomers (for noninferiority < .0001).

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.

At the 2016 Transcathether Cardiovascular Therapeutics (TCT) meeting, where von Birgelen presented 1-year BIO-RESORT outcomes, invited discussant Stuart Spencer, executive editor of the Lancet, commented that "the success rate of PCI is so high that it's very, very difficult to find differences between stents, procedures, and so on," and proposed that 5-year outcomes data will likely be needed before significant differences, if any, emerge.

Here at EuroPCR 2019, von Birgelen reported 3-year outcomes for patients with stents implanted in small vessels for whom follow-up data were available (1452 of 1506 participants with small vessel disease).

Target lesion failure occurred in 7% of patients who received the sirolimus-eluting stent, 9.5% who received the everolimus-eluting stent, and 10% of who received the zotarolimus-eluting stent. There were no significant differences in TLF between the zotarolimus-eluting device and either of the other two stents.

As noted before, however, there was a significant difference in TLR between the sirolimus- and zotarolimus-eluting stents (2.1% vs 5.3%; HR, 0.42; P = .009).

A landmark analysis also showed that the significant difference between the sirolimus- and zotarolimus-eluting stents emerged between 1 and 3 years of follow-up.

Experts Weigh In

Invited discussant Robert Byrne, PhD, German Heart Center Munich, commented that study results from the Twente group are generally well regarded in the interventional cardiology community because of their relatively large size, broad inclusion criteria, and use of common devices that reflect real-world conditions rather than the rarified circumstances of many trials. He took issue, however, with the labels of "ultra-thin" (Osiro) and "very thin" (Synergy) struts, remarking that the distinction is largely arbitrary.

He noted that "small vessels are certainly a good stress test for stents," and that the results show "some evidence of a gradient of effect across the three treatment groups, but it's really when you looked at the three secondary end points that you saw the findings that were significant, and of course the focus was on the positive finding for target lesion revascularization," he added

He also said that the results of this subanalysis still need to be interpreted with caution because of the multiple hoops the data had to jump through, with both 1- and 3-year data, study of a subpopulation, and emphasis on secondary end points.

In an editorial accompanying the results in JAMA Cardiology, Ajay M. Kirtane, MD, Columbia University Medical Center, and Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai, both in New York City, commented that strut thickness appears to make a difference when the target vessel is small.

"This is relevant because it supports the hypothesis that the comparative contribution of stent strut thickness may be greatest among vessels that are not adequately sized to tolerate thicker-stent struts with the greater degree of intimal hyperplasia that may result from these devices," they write.

They caution, however, that "thinner may not always be better, as a randomized trial of the same thin-strutted DES studied within the BIO-RESORT trial failed to demonstrate non-inferiority of this device when used to treat chronic total occlusion lesions that perhaps require a greater degree of radial strength."

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. Byrne reported financial relationships with Boston Scientific and Celonova Biosciences. Spencer reported he had no relevant financial relationships.

JAMA Cardiology. Published online May 21, 2019. Full text, Editorial

Congress of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR) 2019. Presented May 21, 2019.

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