Newer, Thinner-Strut Abbott Scaffold Prompts Talk of a BVS Comeback
There’s no getting around the need for a costly long-term, large-scale clinical trial to show new devices are safe, say experts.
NATIONAL HARBOR, MD—The Absorb bioresorbable scaffold may not have panned out in large randomized clinical trials, but that doesn’t mean the technology is dead or that companies are necessarily put off future studies, say experts. But they caution that moving the field forward will be challenging.
In a relatively quiet move, Absorb’s manufacturer, Abbott, has already returned with a new device, one with struts considerably thinner than the company’s first-generation product. Unlike the Absorb bioresorbable vascular scaffold (BVS or BRS), which had a strut thickness of 150 µm, the Espirit scaffold, has a strut thickness ranging from 100 to 120 µm depending on the stent size.
In a CRT 2020 session devoted to the future of BVS technology, Abbott’s Richard Rapoza, PhD, discussed their new product, which will be tested in a US Food and Drug Administration investigational device exemption study. Known as the LIFE-BTK trial, 225 patients with peripheral disease in the infrapopliteal arteries will receive the Espirit scaffold or percutaneous transluminal angioplasty. Like Absorb, the Espirit BVS is recommended for vessels with a reference diameter from 2.5 mm to 3.75 mm.
In below-the-knee disease, said Rapoza, BVS technology is an attractive potential treatment option because it strikes the “sweet spot” where the device would establish a cylindrical vessel shape that would be sustained for a few years, help modulate with vessel patency with the use of a drug, and then eventually be resorbed so that it wouldn’t interfere in future interventional procedures which are often necessary in patients with symptomatic critical limb ischemia.
Not unlike the use of BVS in the coronary arteries, Rapoza said, implantation with Espirit requires meticulous planning.
If we went back into the coronary arteries, we would require imaging [along with PCI]. We’re not making that mistake again. Richard Rapoza
“I can’t emphasize this enough,” he said. “These patients need to [have] a near-perfect angioplasty before the scaffold is implanted. Secondly, we need to emphasize that the implantation technique is thorough and accurate. . . . We need to be very, very careful in how we size the vessel and how we implant the scaffold so we make sure that the mechanism of action at play in a dynamic scaffold respects the natural processes and the dangers of scaffolds that disappear.”
Alexandre Abizaid, MD (Instituto Dante Pazzanese de Cardiologia, São Paulo, Brazil), one of the session moderators, asked the question on everybody’s mind: whether Abbott would test the Espirit scaffold in patients with CAD.
“If we went back into the coronary arteries, we would require imaging [along with PCI]. We’re not making that mistake again,” said Rapoza. “We need to make sure that in the process we have enough centers that know how to do imaging thoroughly. It doesn’t necessarily need to be [optical coherence tomography]. We have to have a system where the device is implanted accurately and not just with visual assessment.”
Taking a critical lens to that approach, panelist Michael Haude, MD, PhD (Städtische Kliniken Neuss, Germany), said that while intravascular imaging is critical to help learn about the next-generation scaffolds, future devices need to be able to be implanted safely and effectively without imaging.
“When we look clinically, we have to appreciate that we are far from the setting where intracoronary imaging is standard of care in our cath labs,” said Haude. “When I speak for Europe, this is absolutely not the case. When you look at the penetration of imaging there, it’s less than 20%. We need to create something to move into the market once we have noninferiority, that can be done without the addition of more expense.”
Importance of Investigator-Initiated Trials
The Absorb story is well known by now. Despite showing noninferiority when compared with the Xience everolimus-eluting stent (Abbott) at 1 year in ABSORB III, which led to an FDA approval, the 3-year follow-up from ABSORB II showed the scaffold was associated with a twofold increased risk of device-oriented clinical events, specifically an increased risk of target-vessel MI, as well as an increased risk of late scaffold thrombosis compared with Xience. Safety concerns came to the fore in AIDA as well as in several meta-analyses, and the scaffold was eventually discontinued.
In the CRT session, experts involved in testing BVS provided updates on several research programs, such as the Magmaris bioresorbable magnesium scaffold (Biotronik) and Fantom Encore (Reva Medical), as well as the global pipeline. To date, there are six devices approved for use in Europe, but the enthusiasm just isn’t what it used to be after Absorb. The European Society of Cardiology/European Association for Cardiothoracic Surgery (ESC/EACTS) downgraded the use of bioresorbable scaffolds in their newest clinical guidelines for myocardial revascularization, stating that the devices should not be used in practice but only in clinical trials (a class III recommendation).
Speaking during the session, Robert Byrne, MD (Mater Private Hospital, Dublin, Ireland), who led a European task force evaluating the use of BVS in PCI, focused on some of the lessons learned from the ABSORB clinical trials. For him, one of the big questions from the Absorb BVS story is why the preclinical studies didn’t offer any hints of the later risks, such as those associated with late scaffold dismantling.
“I don’t have an easier answer,” said Byrne. “There were a couple of signals when we dig down and look at the animal studies, but it’s a difficult problem to solve.”
Abbott might not be happy to hear that, but there’s just no way that [BVS] are ever going to be accepted without a large trial. Gregg Stone
Byrne stressed the importance of independent, investigator-initiated clinical trials, noting that these studies make an important contribution to postmarketing follow-up and should be supported to provide information in parallel with industry-funded studies. He cited AIDA as a good example, noting that investigators included longer-term follow-up as part of their study and eventually identified a safety concern with Absorb. Such investigator-initiated studies often have greater external validity and generalizability for physicians than industry trials, said Byrne. Going forward, lengthier studies will be needed, he said.
“When we look at the approval study for the Absorb scaffold at 1 year, although there was some separation of the curves with regards to target lesion failure, the differences weren’t statistically significant,” said Byrne. “Then when you follow these patients long-term, and the AIDA trial is a study that had longer-term follow-up built into the primary analysis, we’re clearly seeing that as we got out past 12 months the curves were continuing to diverge.”
Abizaid said physicians, researchers, and scaffold manufacturers are trying to balance moving the technology forward with ensuring patient safety. In an ideal world, studies would be 5 years long, include thousands of patients, and mandate intravascular imaging and serial follow-up, but that’s just not realistic given the massive costs of such studies, said Abizaid.
Large-Scale Trials Needed
Discussing future trials, ABSORB investigator Gregg Stone, MD (Icahn School of Medicine at Mount Sinai, New York), said that in a best-case scenario, it might be possible to conduct a study with a “couple hundred” patients in a small series, provided intravascular imaging with optical coherence tomography was used to achieve excellent implantation success. However, he said, large-scale clinical trials are still going to be needed.
“Abbott might not be happy to hear that, but there’s just no way that [BVS] are ever going to be accepted without a large trial really proving they’re safe in the early period,” he said.
Despite the setbacks, Stone remains a believer in the technology. With permanent contemporary drug-eluting stents, “there is no free lunch,” he said and pointed to their recent patient-level meta-analysis showing that very late stent-related events, including ischemia-driven TLR and stent thrombosis, occur at a rate of roughly 2% per year with no evident plateau in risk. For a 50- or 60-year-old patient who will have the stent for 20 or 30 years, that’s a problem.
“That’s why bioresorbable scaffolds were developed,” he said.
To TCTMD, Arnav Kumar, MD (Emory University School of Medicine, Atlanta, GA), said he is optimistic BVS will succeed in the treatment of CAD.
“We often forget that in ABSORB III we compared a first-generation BRS with a DES that was fairly advanced and had gone through many iterations,” said Kumar. “BRS designs are improving. Already we are seeing that newer-generation BRS have thinner struts with shorter strut height that are associated with a better hemodynamic and shear stress profile.” Some example of these improved scaffolds include the Fantom Encore and Iron BRS (Lifetech Scientific), he said.
Kumar explained that stent deployment changes the geometry of the coronary artery and this is particularly evident when the stent “straightens” a curved vessel. This causes disturbed blood flow and increased strain often at the proximal and distal stent edges, which can lead to low shear stress at these edges. That, in turn, promotes neointimal hyperplasia and can lead to higher rates of restenosis. Just this week, Kumar and colleagues published a paper in EuroIntervention from ABSORB III showing that the BVS was associated with lower shear wall stress compared with Xience.
“A more conformable BRS stent theoretically should induce less change in angulation and curvature compared to metallic stents,” said Kumar. “BRS, once they get absorbed fully, should restore the original vascular geometry and hence result in more streamlined blood flow with physiological shear stress leading to improved outcomes.”
Multiple presenters. BRS: Is there a future for the technology. Presented at: CRT 2020. February 24, 2020. National Harbor, MD.
- Rapoza is an employee of Abbott.
- Abizaid reports financial and grant support from Abbott Vascular, Boston Scientific, Elixir, Reva Medical, and Symetis.
- Haude reports research support, speaking fees, and/or consulting fees from Abbott, Biotronik, Cardiac Dimensions, DSI-Lilly, Orbus Neich, and Volcano.
- Byrne reports speaker’s bureau fees from B. Braun, Biotronik, and Boston Scientific. He reports research support from Boston Scientific and Heartflow.
- Stone reports consulting for Reva Medical, Valfix, Amaranth, and Vascular Dynamics. He reports equity in Guided Delivery Systems and Spectrawave.
- Kumar reports no relevant conflicts of interest.