Big Questions for Bioresorbable Scaffolds: Experts and Innovators Debate

PARIS, France—“Innovation at a crossroads” was the name of a packed session at EuroPCR 2017’s Innovators Day here and while a range of bioresorbable scaffolds were discussed, the biggest questions stemmed from recent disappointments and challenges faced by the front-runner technology, Abbott Vascular’s Absorb bioresorbable vascular scaffold (BVS).

Stephan Windecker, MD (Bern University Hospital, Switzerland), characterized the bioresorbable scaffold technology as “groundbreaking,” but he acknowledged—with quintessential European understatement—it has faced its share of “setbacks.” These include the US Food and Drug Administration’s “Dear Physician” letter warning of an increased risk of major adverse cardiovascular events, as well as the decisions taken in Europe and Australia to restrict use of the device.

As a result, interventional cardiologists here spent the morning discussing everything from implantation techniques to the biomechanical properties of the bioresorbable scaffold relative to best-in-class metallic drug-eluting stents. Chaim Lotan, MD (Hadassah Medical Center, Jerusalem, Israel), took the debate one step further, saying that while the focus during the innovation session was how to improve the bioresorbable technology, maybe a dissolving coronary stent isn’t needed at all.  

“I would like to ask what is the value?” said Lotan. “In other words, what is the unmet need? Is it to have better performance? Is it to have better vasomotor activity?”

With a packed session that included clinical trialists, researchers, and industry, Lotan said the fixation on tweaking the technology might be wrongheaded. “My feeling is that we really don’t have a good unmet need aside from the fact we want this thing to dissolve,” he said. From the very beginning, the cobalt-chromium drug-eluting stent has outperformed the poly-L-lactic acid (PLLA)-based polymer used in the bioresorbable scaffolds, said Lotan.

Jean Fajadet, MD (Clinique Pasteur, Toulouse, France), argued, however, that bioresorbable technology doesn’t need to be better than current-generation drug-eluting stents—he doesn’t think the technology could best drug-eluting stents anyway—but simply to provide equivalent clinical outcomes. “We have younger and younger patients, particularly diabetic patients,” said Fajadet. “We know that there will be a progression of disease. We also know PCI with a drug-eluting stent is not the last intervention for these particularly young patients.”

Given that these individuals are likely to undergo PCI again and again over the years, leaving behind a metal stent in the anatomy is not the best approach for treating progressive coronary disease, he added.

Patrick Serruys, MD (Imperial College, London, England), the lead investigator of the ABSORB II study, came back to an argument made many times in the past, namely that the vessel “needs to move,” which it can’t do with metallic drug-eluting stents. “When you cage the vessel, you open the door for neoatherosclerosis within the cage because you don’t respect basic physiology.”

Moreover, Serruys pointed to the development of the powerful PCSK9 inhibitors, a drug class that is capable of reducing LDL cholesterol down to unprecedented levels, often in the range of 20 to 30 mg/dL. In the GLAGOV trial, as reported by TCTMD, treatment with evolocumab (Repatha; Amgen) resulted in a regression of atherosclerosis as assessed by IVUS. Patients with metallic stents lining the coronary arteries might not experience the full benefits of such plaque regression, said Serruys.

“If you’re there with a cage, you can’t really do too much,” he said. “You reduce your therapeutic options.”

Mechanical Properties of Bioresorbable Scaffolds

Windecker, who facilitated the debate and discussion during the morning session, asked the panelists whether they believed the biomechanical properties of a bioresorbable scaffold could ever match a metallic stent.  

John Ormiston, MD (Mercy Angiography, Auckland, New Zealand), believes these first-generation devices already match metallic devices, at least for the most part. The bioresorbable scaffolds are more flexible than conventional metallic stents and offer similar radial strength, he noted. Although recoil is greater with the BVS, this can be overcome with postdilatation. Deliverability, said Ormiston, remains the biggest challenge with the bioresorbable technology.

Boris Warnack, PhD (Xeltis, Zurich, Switzerland), on the other hand, argued there will always be mechanical property differences between cobalt-chromium and the bioresorbable PLLA polymer, including tensile strength. “There is going to be a difference when you make a scaffold or stent from a polymer versus from high-performing cobalt-chromium or other metallic alloys,” he said. “However, I believe we’re still early in the development of these devices and over time we’re making improvements in working around the material limitations.”

Windecker, for his part, remains optimistic. “If we’re able to build airplanes out of structures that aren’t metal, we could also succeed with stents,” he said.

Regardless of the material used in the scaffold—whether it’s a PLLA- or magnesium-based polymer—the specifications don’t matter nearly as much as the clinical results, said Ron Waksman, MD (MedStar Heart and Vascular Institute, Washington, DC). “It doesn’t have to exactly match the metallic stent,” he said. “It has to be good enough to get us the outcomes of the metallic stent. Just looking into matching the properties [of drug-eluting stents] might be too ambitious.”  

Right now, though, the clinical outcomes of first-generation bioresorbable scaffolds pale in comparison to those with drug-eluting stents, particularly the best-in-class cobalt-chromium everolimus-eluting stent (Xience; Abbott Vascular). As reported by TCTMD, numerous reports, including 3-year data from ABSORB II, have shown the Absorb BVS is associated with an increased risk of device-oriented clinical events, particularly late scaffold thrombosis. In the ABSORB III study, the pivotal study that led to US approval, the 2-year rate of target lesion failure was significantly higher with the Absorb scaffold than with Xience.

Will Thinner Struts Solve the Problem?

One of the questions posed during the session was whether thinner struts in next-generation scaffolds would be more forgiving in terms of reducing late clinical events, specifically risks of scaffold thrombosis and device-related MI. Richard Rapoza, a vice president of research and development at Abbott Vascular, said they are working on developing a second-generation device with struts thinner than the 150-µm struts of the Absorb BVS.

Reducing strut thickness will not solve the issue of late and very late scaffold thrombosis, though. Instead, degradation and structural integrity of the scaffold over time have the largest impact on late clinical events, said Rapoza.

“If we reduce strut thickness, but we don’t change anything else, and we still have severe malapposition from undersizing or underdeployment, we will still have late events,” he said. “That is intrinsic to all [bioresorbable technology], no matter what material you pick. It will degrade and it will fall apart and it has to be embedded in the vessel wall for that process to be benign.”

Given that, Rapoza said that the PSP protocol—an implantation technique that includes preparing the vessel, selecting an appropriately sized device, and postdilatation—will be important even with future scaffolds.

In the end, Waksman said the cardiology community has reached a plateau with metallic drug-eluting stent technology. “Every device that we test, with or without a biodegradable polymer, we get more or less the same results,” he said. “Are we satisfied with that? Is that enough? I would say no. I will tell you that in our center we get at least a patient a day for brachytherapy for [treatment of] restenosis of second-generation drug-eluting stents.”

While the jury is still out on the long-term benefits of bioresorbable scaffolds, a full determination can’t be made until long-term data, that being follow-up of 5 or more years, is available. “Don’t prejudge early-generation devices with some of the shortfalls we’re seeing right now,” said Waksman.

During the interactive session, numerous questions from the audience flashed on the large screen, including whether patients implanted with the Absorb BVS were sufficiently informed about the potential risks of device-related clinical events. Another audience member wondered what it will require for Absorb and other bioresorbable technologies to achieve routine clinical use. Windecker acknowledged these were all good clinical questions for another day.