BIOSTEMI: Ultrathin-Strut Orsiro Superior to Xience for 1-Year TLF After Primary PCI

An ultrathin-strut, biodegradable-polymer DES has demonstrated superiority to a thin-strut, permanent-polymer DES when it comes to target lesion failure at 1 year in patients with acute STEMI, researchers reported at the recent European Society of Cardiology (ESC) Congress 2019.

“After a decade of coronary stent trials with a noninferiority design, BIOSTEMI is the first published head-to-head randomized controlled trial powered for superiority comparing two contemporary and widely used newer-generation drug-eluting stents,” Juan F. Iglesias, MD, PhD (Geneva University Hospitals, Switzerland), who presented the late-breaking BIOSTEMI trial results during ESC, told TCTMD via email.

It’s also the first RCT comparing newer-generation DES specifically in STEMI, Iglesias added. “Despite iterative developments in coronary stent technology, patients with acute STEMI remain at higher risk of patient- and device-oriented adverse clinical outcomes compared to patients with stable coronary artery disease, and determining the optimal drug-eluting stent technology remains an unmet clinical need.”

As to what’s unique about this setting, he explained that the “heightened prothrombotic and inflammatory milieu in patients with acute STEMI poses particular challenges to vascular healing and stent-related clinical outcomes after primary PCI and might reveal the differences among different stent platforms.”

Orsiro received US Food and Drug Administration approval in February 2019 based on the BIOFLOW V trial, which excluded STEMI patients. The device received CE Mark approval back in 2011.

David Kandzari, MD (Piedmont Heart Institute, Atlanta, GA), lead investigator of BIOFLOW V, commented on the latest study for TCTMD. “We thought we had reached a plateau at some point, where all stents were essentially equal in their safety and efficacy. But there is perhaps opportunity to continue to iterate and evolve stent technologies that would translate into a measurable patient benefit,” he said, noting that Orsiro’s performance in BIOSTEMI moves along that same trajectory.

A paper detailing the BIOSTEMI results, with Iglesias and Olivier Muller, MD, PhD (Lausanne University Hospital, Switzerland), as first authors, was simultaneously published online ahead of print in the Lancet.

Is it the Struts or the Polymer?

BIOSTEMI, an investigator-initiated trial, enrolled 1,300 acute STEMI patients (with 1,623 lesions) at 10 centers in Switzerland, randomizing them to primary PCI with either the ultrathin-strut, biodegradable-polymer, sirolimus-eluting Orsiro stent (Biotronik) or the thin-strut, durable-polymer, everolimus-eluting Xience Xpedition/Alpine (Abbott) stent. Twelve-month follow-up data were available for 95% and 96% of the groups, respectively.

As part of the study, Igelsias et al performed Bayesian statistical methods incorporating data on 407 patients from the prior BIOSCIENCE trial. “This approach was prespecified and informed the power calculation of the BIOSTEMI trial, therefore allowing for increased efficiency by reducing the number of participants and trial duration,” they explain. Compared with conventional meta-analysis, “use of robust priors efficiently controlled the type I error rate by downweighting the contribution of historical information from the BIOSCIENCE trial if it turned out to be inconsistent with the information collected in the BIOSTEMI trial.”

By 1 year, the primary endpoint of TLF (cardiac death, target-vessel MI, and clinically indicated TLR) was 4% with Orsiro and 6% with Xience (RR 0.59; 95% Bayesian credibility interval 0.37-0.94). The posterior probability of superiority was 0.986, meaning that Orsiro was 98.6% likely to be superior. This difference in the primary composite was driven by a trend toward fewer clinically indicated TLRs with Orsiro compared with Xience (1% vs 3%).

The individual endpoints of cardiac death, target-vessel MI, and definite stent thrombosis were statistically similar for both treatment groups.

“Planned future subgroup analyses of the BIOSTEMI [trial] will provide further insights into the potential physiopathological mechanisms underlying [Orsiro’s] clinical superiority,” Iglesias noted to TCTMD.

Kandzari acknowledged that it’s impossible to tease out whether this advantage stemmed from strut thickness or polymer biodegradability, though he emphasized that Orsiro’s polymer would still be present within the first year after implantation. Iglesias agreed, noting that “in addition to the polymer coating characteristics, the metallic stent platform composition, geometry, and strut thickness are additional features of the drug-eluting stent design potentially impacting on clinical outcomes in patients with STEMI undergoing primary PCI.”

That said, “the benefits of moving towards thinner-strut stents is really not a new observation,” Kandzari pointed out, citing the BMS era’s ISAR-STEREO trial as well as the DES era’s transition from thicker-strut stainless steel to thinner-strut cobalt alloy devices.

“There’s a strong signal, if you assimilate the data across our history of comparative stent trials, that thinner seems to be better without trading off a cost of scaffolding properties or radial strength, as well,” he asserted. “It highlights [that] a lesser metallic footprint within the artery seems to be associated with promotion of healing, less thrombus formation, and less neointimal proliferation, all of which translates to improved safety and efficacy.”