Absorb Vanishes, but Can Other Bioresorbable Scaffolds Make Magic Happen?

It had a short, albeit highly memorable, run: just a few years in Europe and a mere 14 months on the US market. But in the end the first-generation Absorb bioresorbable vascular scaffold (BVS) didn’t quite live up to the early hype.

Late last week, Abbott Vascular announced they are no longer selling the Absorb BVS effective September 14, 2017, because of “low commercial sales.” While they will continue to work on a next-generation bioresorbable device, the Xience metallic everolimus-eluting stent and the next-generation Xience Sierra will form the “cornerstone” of its portfolio, the company said.

The decision, however, barely caused a ripple in the interventional cardiology community, with physicians having long accepted the “disappearing” stent had but a niche role in clinical practice. For most, the decision to stop selling the scaffold makes sense given data that were tepid at best.

“It’s not too surprising,” Sunil Rao, MD (Duke University School of Medicine, Durham, NC), told TCTMD. “I actually expected it a little earlier than it happened, although I understand there’s probably a lot of deliberation considering the amount of investment.”

Similarly, James McCabe, MD (University of Washington Medical School, Seattle), told TCTMD that Abbott’s decision to stop selling Absorb BVS “didn’t even make waves” because he and his colleagues had already stopped using the device at their hospital. “I do think the data are discouraging but the concept remains intriguing,” he said.

The data are discouraging, but the concept remains intriguing. James McCabe

The failure of Absorb to find a place in clinical practice, which was largely the result of disappointing results from the ABSORB trials, could also have a domino effect on development, said McCabe.

“I don’t know if you’re going to find another company willing to invest billions of dollars into future iterations—that could be a problem—but hopefully we’ll see a future-generation technology that’s a little thinner and performs a little better,” he said.

Boston Scientific has already heeded the warning, announcing in August they stopped the development of their biodegradable vascular scaffold. They specifically cited Abbott’s Absorb BVS as the main reason for their decision, adding that the company feels they’d be better off focusing on making improvements to their existing drug-eluting stent portfolio.

Despite Abbott’s tough run, though, other companies continue to venture onward.

Bad News Started Not Long After Absorb Approved

For the past year, there’s been no shortage of disappointing news from studies evaluating Absorb in clinical trials, including 3-year data from ABSORB II that showed the device was associated with a twofold increased risk of device-oriented clinical events, including target-vessel MI. Data from other studies and registries, such as AIDA, also showed Absorb was associated with an approximate twofold higher risk of scaffold thrombosis. 

This past March, the US Food and Drug Administration issued a “Dear Physician” letter warning of an increased risk of major adverse cardiovascular events and advising physicians not to implant the device in small vessels (as per the label). Regulatory agencies in Europe and Australia restricted use of the device to research settings only.

For Gregg Stone, MD (NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, NY), who led the global ABSORB research program, the decision to stop selling the device makes sense given the low uptake of the scaffold into clinical practice. That low uptake is a response to the “lukewarm” data, said Stone.

In the ABSORB studies, physicians were hampered by structural limitations of the device, he said, but also by not fully appreciating the importance of optimal implantation techniques in their early experiences with the scaffold.

“I do think the outcomes with this first-generation device could be substantially improved if a BVS-specific protocol was used,” said Stone. That protocol includes avoiding small vessels, adequately preparing the lesion, using routine high-pressure postdilatation with noncompliant balloons, and the frequent use of intravascular imaging. Longer-term dual antiplatelet therapy would likely be necessary, too.

“Nonetheless, to some extent, it would have been a difficult pathway to reverse a lot of the negative commentary to date,” he said.

Market Forces: Supply but Little Demand

Still, despite the setbacks, Stone remains a “big believer” in the technology, and he noted that while Absorb won’t be commercially available any longer, researchers are continuing to follow patients in ABSORB III and IV to assess long-term rates of target-lesion failure compared with drug-eluting stents.

Many physicians and patients love the concept of not having a lifelong metal frame in the coronary artery. We’re really just getting started. Gregg Stone

“I do think most people embrace the concept of not leaving anything behind: to have a stent that does its job when it’s necessary, which is really in the first year, and then resorbs completely to allow for more normal restoration of vascular structure and function,” said Stone. “Many physicians and patients love the concept of not having a lifelong metal frame in the coronary artery. We’re really just getting started.”

Adnan Chhatriwalla, MD (St. Luke’s Mid America Heart Institute, Kansas City, MO), told TCTMD that his colleague Barry Rutherford, MD, one of interventional cardiology’s pioneers, once said that in 20 years, “people are going to look back and think this was the Stone Age, where we were literally leaving metal jackets behind in arteries.”

While he is uncertain of the time horizon, Chhatriwalla also believes that metallic drug-eluting stents won’t be the treatment of choice in the future. In the immediate present, though, he appreciates that the low uptake of Absorb in clinical practice left Abbott with no choice but to make their commercial decision.

“A lot of times physicians get a bad rap,” said Chhatriwalla. “We’ve published studies that have been critical of physicians. They have a reputation for not caring about cost and using whatever they think is better or best, even when there isn’t always evidence to show it’s better or best. Here, maybe we should praise physicians for being hard on Abbott, for being hard on the technology.”

Clinical trials with Absorb, he noted, showed “equivalence at best—it’s not a superior technology” and yet the scaffold costs more than conventional drug-eluting stents with a better track record. The market, said Chhatriwalla, forced Abbott back to the drawing board, with physicians essentially demanding a better product.

Absorb accounted for less than 1% of Abbott’s overall stent sales, according to the company. The device has been available in the US since July 2016, in Japan since November 2016, and in Europe since 2011. The decision to stop selling Absorb is global, affecting all countries.   

Uphill Climb for BVS Development

For Rao, the decision to continue working on a next-generation bioresorbable scaffold is a good idea, although he noted that any new or emerging platforms will face a tough challenge.

“It’s amazing how good the stents are today,” he said. “It’s an uphill climb for any company that’s interested in bioresorbable scaffolds now. Not only does the new platform have to compete against existing metallic stents, it has to overcome the limitations of the prior generation BVS.”

Rao pointed to the BIOFLOW V data recently presented at the European Society of Cardiology Congress 2017 showing that the Orsiro “ultrathin-strut” coronary stent (Biotronik) bested the market-leading Xience stent for both 12-month target lesion failure and MI. Those findings weren’t expected, he said, considering how well the Xience stent performs.

While the interventional cardiology community historically has had a degree of tolerance for the pitfalls associated with early technology because new devices addressed specific problems, bioresorbable scaffolds didn’t have that luxury. “Bare-metal stents clearly were addressing abrupt closure. Drug-eluting stents were addressing restenosis,” said Rao. “With BVS, it’s a little more hazy as to exactly what the clinical problem is that they are designed to address.”

To TCTMD, McCabe said that when Absorb became available in the US, patients would inquire about or even request the scaffold, but that honeymoon period didn’t last very long. The low uptake “speaks for itself,” he said, noting that the physicians who no longer used Absorb in practice as most felt it carried “undue risk.”

With BVS, it’s a little more hazy as to exactly what the clinical problem is that they are designed to address. Sunil Rao

“I’m hopeful that if the technology can perform better—and that’s a big if because it’s a high bar; the metallic stents are very good—there is a role for the concept,” said McCabe. He noted that drug-eluting metallic stents also went through a rough patch when concerns were raised about the risk of stent thrombosis. In time, with better technology, those fears subsided. He is hopeful the bioresorbable technology can also overcome its early trouble.

“We’re really struggling with what to do with these people who have two and three layers of metal in similar spots or who are completely coated with metal in all of their coronaries,” said McCabe. “That’s a tough scenario to treat and I’m not sure it would be made perfectly better by having bioresorbable scaffolding, but it wouldn’t burn as many bridges either.”

Getting Better? That’s the Hope

For Stone, the lessons learned from the Absorb scaffold will only serve to help companies build a better mousetrap. “When you get a second-generation device that promises to be much more deliverable, has better expansion characteristics, and thinner struts, it promises to have much lower early-term event rates,” he said. “I think there will be pretty substantial enthusiasm to want to investigate such a device.”

Mladen Vidovich, MD (University of Illinois, Chicago), agreed that the failure of Absorb was disappointing, although he remains optimistic the technology is the future. “We learned a tremendous amount that we simply didn’t know before,” he told TCTMD. “We know about strut thickness, we know how to implant, and we know how to image them now. I think we also learned the right patient population [in whom] to use them. I’m very optimistic the next iteration will have a better safety profile.”

Rao is a tad skeptical, though, noting the major issue to raise red flags with physicians was scaffold thrombosis, which he isn’t certain will be addressed with thinner struts. Moreover, the PSP protocol—prepare the lesion, appropriate size the vessel, and postdilatation—is “just good angioplasty practice, which should apply to almost any stent you put in.” Adhering to the PSP protocol for patients treated with Xience and other drug-eluting stents also results in better outcomes, said Rao.

“It’s high-quality PCI is what that is,” he said. “Thinner struts, I think that’s great. Is it going to solve the entire issue with BVS? I’m not convinced of that.” 

Chhatriwalla hopes Abbott responds to the cardiology community and makes significant design changes, which will hopefully facilitate better outcomes. As for physicians, even early adopters, they are going to remain appropriately skeptical with future products, and will likely want to know if the newer-generation BVS are “superior in some way.”

“Do we need longer-term outcomes to do that, or different outcomes, than the traditional MACE endpoint, which is simply heart attacks, and death, and urgent revascularization?” he asked. “Some of the theoretical benefits of the bioresorbable technology are not those outcomes.”

Still, if future data is solid, physicians will return to BVS technology. “You’ve got to show it’s got some benefit,” Chhatriwalla said. “If you can show that, then I don’t think there’s any reason why it can’t win physicians over.”

Just like going from the combustible gas engine to the electric car, bumps in the road are to be expected, said Stone. “Even the first-generation Tesla model had a lot of setbacks and was not widely embraced, but you can see what’s happening now with contemporary Tesla—it’s really changing the whole world.”