Absorb in Europe: When, How, and by Whom the Beleaguered BVS Is Being Used After Restrictions

Last month the Absorb bioresorbable vascular scaffold (BVS) was removed from the shelves of many centers across Europe and then also in Australia after Abbott Vascular, working with local regulators, announced that its use would be restricted to sites participating in clinical trials and registries.

What remains unclear is just how many hospitals will still be implanting the device while scaffold thrombosis remains a concern and the long-term trade-off has not been established. From the outset, Abbott has stated that the “vast majority” of centers using Absorb will continue to do so, but as TCTMD learned, the actual number is difficult to pin down.

Several European cardiologists who spoke with TCTMD say that use of Absorb BVS had already been on the decline following the worrisome 3-year outcomes from the ABSORB II study. Now, however, use has been even more severely curtailed, if not stopped outright, in their various countries. Many physicians say they are confused about when, or if, they will be able to use the device again in clinical practice. 

Absorbing the News

Stories of how the Absorb device is leaving hospital shelves speak to the uncertainty. Martin Bergmann, MD, PhD (Cardiologicum Hamburg, Germany), is an interventional cardiologist who calls himself an “early and careful” adopter of the Absorb technology. Now working in private practice, Bergmann was previously the director of the catheterization laboratory at St. Georg Hospital in Hamburg, Germany, where he served as the local primary investigator of ABSORB III and enrolled approximately 10 patients in the trial.

In 2014, he moved to his current position and established a scaffold program using Absorb and other bioresorbable devices, including DESolve (Elixir Medical) and Magmaris (Biotronik). His use of Absorb peaked around 2014 when he and colleagues implanted approximately 20 to 30 scaffolds. The overall PCI volume at his center is 950 cases per year.

Bergmann told TCTMD an Abbott representative came to their catheterization laboratory in mid-April and removed all remaining Absorb stock, telling the cardiology group the company did not plan any new registries. Nor did they receive any information on future projects from Abbott management, which left him confused.

“I was really expecting them to come with some new registry,” he said. “I was really caught by surprise that the representative, that we have known for many years, that we have discussed all of these issues [with], told me she was asked just to clear our scaffolds and that there was no registry coming. In my mind, and I’ve discussed this with some colleagues, it really looks like this has been pulled from the market.”

The large German-Austrian Absorb Registry (GABI-R) was closed, Bergmann noted, although it is poised to reopen. Abbott has offered the group participation in this registry, but Bergmann said he’s not convinced that simply reopening it will ultimately address some of the issues around the embattled device, such as the adverse events that occur even when operators are careful when implanting.

Gert Richardt, MD (Heart Center Segeberger Kliniken GmBH, Bad Segeberg, Germany), a member of the GABI-R steering committee, told TCTMD that at the time the registry was open, there were approximately 100 enrolled German hospitals but only 70 were active in implanting the scaffold. His center had enrolled 137 patients, Richardt said.

While the registry is on hold, Richardt said he and his Heart Center colleagues are currently participating in the COMPARE-ABSORB randomized clinical trial. The study, which is being conducted at 47 centers in 10 European countries, including 9 centers in Germany, has a planned enrollment of 2,100 patients at high risk for restenosis who are randomized to Absorb or Xience.

In the UK, Italy, and Spain

Interventional cardiologists in other countries appeared to have similarly mixed views on what the future holds.

In the United Kingdom, Nick West, MD (Papworth Hospital, Papworth Everard, England), told TCTMD that after the CE Mark approval in 2011, rollout of the Absorb BVS was “fairly slow and measured,” with approximately 25 sites participating in the UK registry even though participation wasn’t mandatory. The UK registry is now closed though, and for the moment, the only way to use the device is by participating in one of four clinical trials: COMPARE-ABSORB, DISCRETE-CTO, EMPIRE-BVS, and ABC-ONE, the latter two of which are at single centers.

All told, according to West, there are just nine centers using Absorb in clinical trials. The 1-year UK registry results are scheduled to be presented next week at EuroPCR in Paris, France.

“The curtailment is sizeable,” said West. “It’s not to be underestimated.”

A UK-based registry is expected to launch soon, West said, and surveillance will focus specifically on the optimal implantation technique in an attempt to minimize the risk of adverse events with Absorb. West believes European regulatory agencies have acted responsibly, given the concerns over patient safety, but acknowledges this wasn’t the ideal course of events.

“It would have been nice if the decision about this could have been taken at the front end of the regulatory process—if a large trial and follow-up was needed—rather than get halfway through and decide we need to retrench a bit,” West said.

In Italy, Davide Capodanno, MD, PhD (University of Catania, Italy), told TCTMD there are currently two ongoing studies—the international COMPARE-ABSORB and the nonrandomized CART pilot study, in patients with cardiac allograft vasculopathy—but there are no open registries. Like the UK numbers, data from the Italian ABSORB registry (BVS-RAI) and Italian Diffuse/Multivessel Disease ABSORB prospective registry (IT-DISAPPEARS) will be presented at EuroPCR in a session highlighting the registries and clinical trial updates. At the session, researchers will also present 3-year data from ABSORB-China and ABSORB-Japan. 

Capodanno said the Italian Medicines Agency (AIFA), working in conjunction with the Italian Society of Interventional Cardiology, will ultimately decide if the registries should reopen. “There is a plan, without any definitive conclusions, to reopen [IT-DISAPPEARS] to allow the centers to eventually use the device in this context, but that’s not 100% certain,” he said. The final decision to reopen and extend the registry will be made at the end of May, although he is not optimistic this will happen.

Similarly, Manel Sabaté, MD, PhD (Hospital Clinic de Barcelona, Spain), told TCTMD there is one observational registry in his country, known as REPARA-QALY, with approximately 40 sites participating and only half of these centers having enrolled patients. Given Abbott’s actions in Europe, he is uncertain if the centers that have not yet enrolled patients will continue to participate in REPARA-QALY.

The Company View

For its part, Abbott Vascular is adamant the device is not being withdrawn from Europe, pointing out that the scaffold retains CE Mark approval. Asked for hard numbers on centers still implanting, an Abbott spokesperson confirmed that there are currently 12 open registries covering 114 sites in Europe and three more registries are confirmed to open in the coming weeks in Germany, France, and the United Kingdom.

“We believe a total of 15-20 registries that include select hospitals in 14 countries will cover the vast majority of current Absorb use in the European Union,” according to the Abbott spokesperson, adding that the final number of registries and sites won’t be determined until after May 31 and that the studies are investigator-sponsored. The decision on whether to participate will depend on discussions with respective local health authorities and on each site’s “data collection abilities, reporting capabilities, and physician experience with Absorb,” she said.

To put those figures in perspective, the European Society of Cardiology says there are 2,008 PCI-capable sites in Europe, excluding the United Kingdom and Georgia. In the UK, based on 2014 data from the British Cardiovascular Intervention Society, there are another 119 PCI-capable sites: 102 centers in England, 8 in Scotland, 4 in Northern Ireland, and 5 in Wales.

So, while Abbott’s “vast majority” refers to the number of previously implanting sites that will continue to implant, after May 31 the proportion of European PCI-capable hospitals that will have the device on their shelves appears to be somewhere in the vicinity of 5%.

What Comes Next

The oft-stated rationale for limiting Absorb use to sites participating in trials and registries is that these are the operators with the most experience and who are likely to understand the importance of optimal technique. Proponents of Absorb say the risks can be attenuated with good implantation techniques—the so-called PSP protocol (preparing the vessel, adequate sizing, and postdilatation).

Indeed, the principal recommendation of a US Food and Drug Administration (FDA) safety alert sent to physicians in March 2017 was to closely follow package instructions regarding target vessel selection—avoiding BVS use in vessels smaller than 2.5 mm and ideally using intravascular ultrasound (IVUS) and optical coherence tomography (OCT) to optimally size the vessel.

Some analyses have hinted that the PSP protocol will lead to improved outcomes with ABSORB, but not everyone is certain this will be the magic bullet. Bergmann, who no longer has the scaffold on his hospital shelves, said that nearly all of the Absorb scaffolds he and his colleagues previously implanted, including during ABSORB III, were deployed with special attention paid to technique under OCT guidance.

As such, even before the restrictions went into place, Bergmann said that use had declined “in my lab as well as many other labs because everybody had experienced, even with ideal implantations, some unpredictable scaffold thrombosis. The feeling was that if we had implanted a drug-eluting stent, there wouldn’t have been a problem.” In fact, he added, they have observed scaffold thrombosis despite OCT guidance and ongoing dual antiplatelet therapy—most often with the 2.5 mm device but not limited to this size—as early as 4 weeks after implantation and as late as 13 months. He said he relayed this information to Abbott.

“My take on the story is now firmly that it needed the FDA action, though we had reported similar events to those observed in the study early on in the adoption of the technique here in Germany,” said Bergmann. “In retrospect, it looks like this didn’t make any impact on their marketing strategy,”

West, speaking with TCTMD, pointed out that while everyone is talking about Absorb, it remains to be seen what happens with other bioresorbable scaffolds being used in Europe. It will be interesting to see if there are the “same curtailments and restrictions applied to those devices,” West said. “Or are we just going to wait until we’re 4 years down the track?”

In the wake of the European restrictions there are questions over whether the FDA should follow suit and limit use of Absorb to clinical registries and ongoing trials. For now, however, the stent remains available to practicing physicians outside of research settings.

At least one US interventionalist believes Abbott should launch a postmarketing registry study to understand how the device is currently being used. “The challenge is that as the bad news comes out from other countries, [Absorb] BVS use will decrease in the US and there won’t be enough ‘real world’ use to generate enough data,” Sunil Rao, MD (Duke Clinical Research Institute, Durham, NC), commented in an email to TCTMD. “Limiting its use to just trials is also a double-edged sword because a potential research patient has to be fully informed of the risks, including the fact that the device has been limited to trial use in other countries.”

As a result, enrollment in such trials will be difficult, which in turn may create a scenario where there are insufficient data to draw firm conclusions. “Certainly long-term follow-up from the pivotal trials is a necessity if the technology is to be saved or improved,” said Rao.