CORRECTION: Polymer-Free BioFreedom Stent Faces Off Against Orsiro

SAN DIEGO, CA—***EDITOR'S NOTE: The following story was written at the time of SORT-OUT IX's presentation at TCT 2018. It subsequently came to light that the data presented contained statistical inaccuracies that changed the primary endpoint. We have subsequently published an explanation of the changes, which affects the accuracy of the story which follows. The version of record can be found here.***

A head-to-head comparison of two different stent technologies in all-comers patients showed that both were equally safe, but the polymer-free biolimus A9-coated BioFreedom stent was not as nearly as effective as the Orsiro ultrathin-strut drug-eluting stent.

Presenting the results of SORT-OUT IX at TCT 2018 during a late-breaking trial session, Lisette Okkels Jensen, MD (Odense University Hospital, Denmark), reported that while the polymer-free BioFreedom stent (Biosensors) was “noninferior” to the Orsiro stent (Biotronik) for the trial’s primary endpoint, it was associated with a significantly increased risk of target lesion revascularization.

In terms of the primary endpoint—a composite of cardiac death, target lesion-related MI, or target lesion revascularization—the two stents were equivalent, with an event rate of 5.3% in the BioFreedom arm and 4.0% in the Orsiro group (P = 0.01 for noninferiority). The rate of definite stent thrombosis was 0.7% in both treatment arms.

For Jensen, though the BioFreedom stent wasn’t as effective as the ultrathin-strut Orsiro, the trial should provide peace of mind to physicians who choose to use the biolimus A9-eluting polymer-free stent in these types of patents, the majority of whom presented with acute coronary syndrome.

Giulio Stefanini, MD (Humanitas University, Milan, Italy), who wasn’t involved in the study but was a panelist during the session, agreed with those conclusions. 

“It reassures us about the safety profile of the BioFreedom device,” he said. “If we look at the event rates of definite stent thrombosis—both definite and probable stent thrombosis—the event rates of SORT-OUT IX are perfectly in line with other drug-eluting stent all-comer trials. There had been concerns after LEADERS FREE because of the high event rates, but I think we can say that the high event rates in LEADERS FREE were due to the high-risk population and not the device. I think this is an important message of SORT-OUT IX—the device is safe.”

In LEADERS FREE, a trial that included patients at high risk for bleeding, the BioFreedom stent was shown to be superior to bare-metal stents, but the 1-year composite endpoint of cardiac death, MI, or stent thrombosis occurred in 9.4% of patients treated with the polymer-free device. Clinically driven target lesion revascularization was observed in 5.1% of the BioFreedom-treated patients.

BioFreedom and Orsiro have important differences. Whereas Orsiro is an ultrathin-strut stent (60 to 80 µm depending on stent size) with a bioresorbable poly-L-lactic acid polymer, the polymer-free biolimus A9-eluting stainless-steel device is relatively thick at 120 µm. Philip Urban, MD (La Tour Hospital, Geneva, Switzerland), said he believes the higher rate of target lesion revascularization in SORT-OUT IX is likely attributable to stent deliverability and strut thickness.

“It’s very reassuring from a safety point of view, but the [inferior] efficacy, we have to admit, is [due to] strut thickness,” he said. “That’s the most likely explanation. It fits with ISAR-STEREO, which was the most solid piece of data telling us that this was the effect of thick struts.”

Less Efficacy With BioFreedom

Speaking during a press conference, Jensen said the persistence of a polymer in first- and second-generation drug-eluting stents has been suggested to be a trigger of the chronic inflammatory response that can lead to adverse outcomes, particularly stent thrombosis. In patients with an increased bleeding risk—a group of individuals unable to tolerate prolonged dual antiplatelet therapy—a polymer-free drug-coated stent has been considered a potential treatment option. 

In SORT-OUT IX, investigators enrolled slightly more than 40% of patients undergoing PCI for stable angina and the remainder for STEMI and NSTEMI/unstable angina. Approximately 25% of patients in both arms underwent PCI for STEMI. The recommended dual antiplatelet therapy regimen included 6 months of aspirin and clopidogrel in those with stable angina and 12 months of aspirin and ticagrelor/prasugrel for those with acute coronary syndrome.

In total, 3,151 patients were randomized to treatment with the biolimus A9-eluting BioFreedom stent or the sirolimus-eluting Orsiro stent. At 1 year, BioFreedom was noninferior to the Orsiro stent regarding the primary endpoint, but the rate of target lesion revascularization favored the thin-strut Orsiro stent (1.3% vs 3.5%; RR 2.77; 95% CI 1.66-4.62).

Sigmund Silber, MD, PhD (Heart Center at the Isar, Munich, Germany), another panelist during the late-breaking trial session, questioned the extent to which clinical practice should change in light of these and other data. In ReCre8, for example, another all-comers study presented in the same session and reported on by TCTMD, investigators showed that a polymer-free amphilimus-eluting stent (Alvimedica) was noninferior with regard to target lesion failure at 12 months compared with the Resolute Integrity zotarolimus-eluting stent (Medtronic).  

“For me, what’s important is when I come back to Munich after this meeting to ask: what would I do differently?” said Silber. “Could you tell me one reason why I should switch to a polymer-free drug-eluting stent, since they are even more expensive than the established durable-polymer stents?”

Jensen again stressed device safety and pointed out they did not randomize patients to a short duration of dual antiplatelet therapy, nor did they specifically include patients at high risk of bleeding, which is potentially where the advantage of the device lies. Sunil Rao, MD (Duke University Medical Center, Durham, NC), told TCTMD that a study comparing a thin-strut stent, such as Orsiro, against a polymer-free drug-coated stent in patients at high risk for bleeding would be ideal.  

“If you look at LEADERS FREE and LEADERS FREE II, those are both against bare-metal stents,” said Rao. “The logical question that arises is what happens if you use a regular thin-strut drug-eluting stent against a relatively thick-strut biolimus A9-eluting stent. They didn’t test it in a patient population at high risk for bleeding—I’m not really sure why—so I think the results are expected. If you have a thin-strut versus a thick-strut stent, one would expect TLR to be lower in the thin-strut stent arm. I think this probably sets up the next series of trials, which would be a high-bleeding-risk population.”

For Antonio Colombo, MD (San Raffaele Scientific Institute, Milan, Italy), the BioFreedom stent would only be used in patients unable to tolerate dual antiplatelet therapy because of a high risk of bleeding. The inferior efficacy, but similar safety, compared with the ultrathin Orsiro stent in this patient population is “totally expected” and “not surprising” given the difference in strut thickness, he said.