'Ridiculous' (in a Good Way) Results With Novel Stent

Neil Osterweil

September 23, 2018

SAN DIEGO — Two stents — one a thin-strut model designed for improved visibility on imaging and the other a polymer-free drug-coated metal design crafted for patients at high risk for bleeding — went head to head against the same formidable opponent in randomized all-comers trials, and both novel devices were found noninferior to the not-so-old standby.

In the BIONYX trial, a thin composite wire strut durable polymer-based drug-eluting stent (DES; Resolute Onyx, Medtronic) was found to be noninferior to the bioresorbable polymer-coated sirolimus-eluting Orsiro stent (Biotronik) for the primary composite endpoint of target-vessel failure, a composite of cardiac death, target-vessel–related myocardial infarction, or clinically driven target-vessel revascularization at 1 year in all comers, reported Clemens von Birgelen, MD, PhD, Thorax Centrum Twente, Enschede, the Netherlands.

Both the Resolute Onyx and Orsiro devices were associated with a low rate of stent thrombosis, but the 0.1% rate seen with Resolute Onyx, compared with 0.7% for Orsiro, was called "ridiculously low" by invited discussant Stuart Spencer, senior executive editor of The Lancet, where the results were published to coincide with von Birgelen's presentation of the data here at Transcatheter Cardiovascular Therapeutics (TCT) 2018.

While von Birgelen cautioned that the stent thrombosis findings were hypothesis-generating only, "the observed very low rate of stent thrombosis in the Resolute Onyx arm warrants further clinical investigations."

In the SORT OUT IX trial, conducted at four centers in Denmark, investigators compared the Orsiro stent with a novel polymer-free coronary biolimus A9–coated polymer free stent (BioFreedom, Biosensors International), which is currently available in Europe but not in the United States or Canada.

Like the Resolute Onyx stent, the BioFreedom device was also found to be noninferior to the Orsiro stent, but the polymer-free stent was associated with a numerically 1.3% higher rate of target lesion failure, the primary endpoint.

"The BioFreedom stent had similar safety with similar cardiac deaths, similar myocardial infarction, and risk of definite stent thrombosis as the Orsiro stent," said Lisette Okkels Jensen, PhD, Odense University Hospital, Denmark. "However. the efficacy was lower in the BioFreedom stent, where we saw a higher risk of target-lesion revascularization compared with the Osiro stent."


The Resolute Onyx stent was designed to solve the problem of limited radiographic visibility that can occur with devices that have circular cobalt-chromium struts, von Birgelen said. 

The device consists of a thin strut composite wire stent platform that is covered with a zotarolimus-eluting durable polymer coating.

"The metallic stent platform consists of a composite wire made from a dense platinum–iridium core, which makes the struts radiopaque, and an outer layer of cobalt–chromium alloy. The dense core also allows for reduced strut thickness, which might be associated with a decreased risk of stent thrombosis," the investigators explain in the published version of the study.

The trial, conducted at seven centers in Belgium, Israel, and the Netherlands, involved 2488 patients, 1243 of whom were assigned to receive the Resolute Onyx stent, and 1245 of whom were assigned to the Orsiro stent.

They chose the Orsiro sirolimus-eluting stent for the reference device because of its excellent safety and efficacy outcomes in three all-comer trials, and for its superior performance against the formed best-in-class everolimus-eluting stent in the BIOFLOW V trial, von Birgelen said in a briefing prior to his presentation.

Rates of target-vessel failure were 4.7% in the Orsiro arm and 4.5% in the Resolute Onyx arm. The absolute risk difference was 0.2%, well below the 1.1% upper limit of the one-sided confidence interval meeting the criteria for noninferiority (P for noninferiority = .0005). The Resolute Onyx stent did not, however, meet the prespecified boundary for superiority.

At 1-year follow-up, there was no statistically significant difference between stent groups in any of the components of the composite endpoint.

Also as noted, the incidence of definite or probable stent thrombosis was 0.7% with the Orsiro stent vs 0.1% with the Resolute Onyx device.

The rate of the primary endpoint was lower than the rate of 6% at 1 year assumed to calculate the sample size, von Birgelen acknowledged, but he added that underreporting of events is not likely, given the use of systematic biomarker and electrocardiographic assessment, an extraordinary 99.6% retention rate for follow-up, and the use of independent monitoring and event adjudication in the trial.

Following the presentation, The Lancet's Spencer commented that the editors chose the study because they were impressed by the trial's high success rate, "ridiculously high" retention rate, and the aforementioned "ridiculously low" stent thrombosis rate.

How much further do we have to go to get below 0.1% stent thrombosis? Dr Stuart Spencer


"That really made us stop and think whether this was really perhaps an indication that we've reached the end of the comparisons of stents in this way. How much further do we have to go to get below 0.1% stent thrombosis?" he said.

Invited discussant Tullio Palmerini, MD, University of Bologna, Italy, said that the findings of BIONYX are consistent with other studies showing that outcomes are similar between durable polymer and bioresorbable polymer stents.

"Probably it's the platform that is going to make an improvement," he said. "There are data coming from randomized trials, meta-analyses, that suggest that with thinner struts you may lower the rates of target-vessel failure and stent thrombosis."  

Discussant Jens Flensted Lassen, MD, PhD, Aarhus University, Denmark, suggested that Resolute Onyx device's better radiographic visibility might have contributed to the low stent thrombosis rate.


SORT OUT IX was a randomized, multicenter, single-blind study noninferiority study comparing the BioFreedom polymer-free device with the Orsiro stent in 3151 patients with chronic stable coronary artery disease or acute coronary syndromes. There were no restrictions on the number of treated lesions, treated vessels, or lesion length.

The clinical event–driven trial was designed to take advantage of Denmark's all-encompassing birth-to-death health registries, linking individual patients with data on deaths (cardiac or noncardiac), hospital admissions, revascularization, and complications.

The BioFreedom device is composed of stainless steel with 120 micron–thick struts, coated with biolimus A9. The device release 98% of the drug over 28 days, putting it in a category midway between a coated device and DES, Jensen said.

Of the 3151 patients enrolled, just 5 were lost to follow-up (from emigration) after 1 year, leaving 1570 patients in the BioFreedom group and 1576 in the Orsiro group available for analysis.

The primary endpoint of target lesion failure at 1 year, a composite of cardiac death, myocardial infarction related to the index lesion, and target-lesion revascularization, occurred in 5.3% of patients assigned to receive the BioFreedom stent, compared with 4.0% in those assigned to receive the Orsiro device (P for noninferiority = .010).

Cardiac deaths occurred in 1.2% of patients in the BioFreedom group vs 2.1% in the Orsiro group. The rate ratio of 0.57 was not statistically significant. Myocardial infarction rates at 1 year were also similar between the groups, at 2.5% and 2.4%, respectively.

Rates of definite stent thrombosis were identical between the groups, at 0.7%, as were rates of definite/probable stent thrombosis, at 1.1% in the Orsiro group vs 1.0% in BioFreedom group.

However, significantly more target-lesion revascularizations were required in the polymer-free stent groups, at 3.5% compared with 1.3% for the Orsiro group. This translated into a rate ratio of 2.77 (P < .0001).

David J. Cohen, MD, MSc, University of Missouri-Kansas City, an invited discussant at a briefing where Jensen presented her data before her presentation, told theheart.org/Medscape Cardiology that the BioFreedom device "is for patients in whom you are not comfortable giving them more than a month of DAPT [dual antiplatelet therapy].

"If you can give 6 to 12 months of DAPT, the data would say that a conventional polymer-based drug-eluting stent is better with respect to stent restenosis and target-vessel revascularization at a minimum, which is the whole reason we use drug-eluting stents in the first place," he said.

Discussant Giulio Stefanini, MD, Humanitas University, Milan, Italy, commented that the study provides reassuring data about the safety of the BioFreedom device.

"If we look at the event rates of both definite or probable stent thrombosis, the event rates of SORT OUT IX are perfectly in line with other DES all-comer trials," he said, adding that the high event rates seen in a different trial of a polymer-free stent, LEADERS FREE, were due to the high-risk patient population and not to the device itself.

The BIONYX Trial was supported by Biotronik and Medtronic. von Birgelen disclosed grant/research support from the companies and others. Spencer reported no disclosures. Palmerini reported fees, honoraria, and speakers bureau participation for Abbott Vascular. Lassen reported having nothing to disclose. SORT OUT IX was sponsored by Odense University Hospital; no study funding source was disclosed. Jensen disclosed grant/research support from Biotronik, Biosensors, and St. Jude Medical. Cohen disclosed grant/research support from Abbott Vascular, Boston Scientific, Edwards Lifesciences, Medtronic, Corvia Medical, and Svelte Inc and fees from Edwards and Medtronic. Stefanini disclosed grant/research support from Boston Scientific and fees from that company as well as B. Braun and Biosensors.

Transcatheter Cardiovascular Therapeutics (TCT) 2018. Late-breaking clinical trial abstracts. Presented September 22, 2018.

Lancet. Published online September 22, 2018. Abstract  

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