The Bioresorbable Stent Story So Far: What Promise? What Price?

It’s a little bulkier, with thicker struts, and is nowhere near as refined as the sleeker, more mature permanent-scaffold drug-eluting stents widely in use. But as the Absorb GT1 bioresorbable vascular scaffold (BVS, Abbott Vascular) makes its debut in the United States, it’s being met with curiosity and enthusiasm for what many believe is an exciting new chapter in coronary disease care.

Earlier this summer, the US Food and Drug Administration (FDA) approved the Absorb BVS, making it the country’s first commercially available bioresorbable stent. For interventional cardiologists here, the introduction of the stent into clinical practice—more than half a decade after their European counterparts began using it—is a welcome advance.

TCTMD set out to ask physicians with little or no previous experience with the new device about their hopes and fears as the Absorb story unfolds. We also spoke with experts who are already part of the plot, having participated in Absorb studies or undergone training, and now using the stent in their clinics.

One overarching question is on everyone’s mind: until the theoretical advantages of a dissolving stent have been proven, what will hospitals have to pay for a first-generation product that is trickier to use but—at least for now—no better than the stents already on their shelves?

Cost Considerations

In ABSORB III, the Absorb BVS was shown only to be noninferior on the primary endpoint of target lesion failure compared with Xience at 1 year (7.8% with Absorb vs 6.1% with Xience; P = 0.007 for noninferiority and P = 0.16 for superiority). The potential advantages of a dissolving stent, however, would not be expected to bear fruit until 2, 3, or even 5 years down the road.

For competitive reasons, Abbott has not disclosed the cost of the stent in the United States so exact prices are difficult to pin down. In Europe, different hospital systems within each country pay a different price, including different prices relative to the cost of existing metallic DES. TCTMD surveyed a range of cardiologists—all of whom spoke on the condition of anonymity and none of whom are quoted in this story—on the absolute and relative costs of the device.

“I think it's no different than when patients come in to the office for blood pressure checks and they’re on antihypertensive medication—they want to be on the cheapest drug and it’s important to them.”

One German cardiologist told TCTMD his center pays as little as 90€ ($100 USD) for a metallic DES, noting that his hospital is part of a large consortium and negotiates very aggressively on the cost of devices. In contrast, they pay approximately 10 times that price for Absorb. Another interventional cardiologist told TCTMD that DES typically cost less than 200€ ($220 USD) in other German hospitals while Absorb is priced around 1500€ ($1,700 USD), or seven times higher.

In the United Kingdom, one physician said there is “quite a big markup” over Xience (Abbott Vascular) and Resolute (Medtronic), which limits use of Absorb BVS within the National Health Service. Another, however, told TCTMD that DES in the UK are quite inexpensive, with Xience, Resolute, Biomatrix (Biosensors International), and others costing approximately £280 to £350 ($360 to $450 USD). While the cost of Absorb varies from hospital to hospital within the UK, it generally costs between £700 and £1,000 ($900 to $1,300 USD). 

In contrast, the relative markup of Absorb BVS over DES in countries like Italy and Austria, for example, is much less, with DES costing approximately 900€ and the new device 1100€ ($1,000 vs $1,200 USD), according to one interventional cardiologist.

In the United States, the price of Absorb will be negotiated between Abbott and the various hospital systems. Such negotiations are par for the course between device companies and hospital administrators, with the final price paid per unit depending on a variety of factors, not the least of which is volume.

Several US doctors told TCTMD that Abbott appears to be adopting a strategy where the cost of Absorb is competitive with existing metallic DES technology, all with the hope of gaining market share. Again speaking on the condition of anonymity, several have pegged Absorb as costing anywhere from $100 to $200 more than the Xience DES, saying the new BVS technology costs in the range of $1,200 to $1,500. One cardiologist told TCTMD they pay a “small premium but the price is close to other latest generation DES.”

In addition to the cost of the Absorb stent, there are other aspects of the procedure that can add up, including the use of IVUS or optical coherence tomography (OCT). For example, in small vessels (those with a visually assessed diameter ≤ 2.75 mm), use of online quantitative angiography, IVUS, or OCT is strongly recommended to accurately measure and confirm vessel sizing. If atherectomy devices are used to prepare the vessel for Absorb, along with the regular use of postdilatation balloons, this contributes to the higher costs of the procedure, they note.

Speaking with TCTMD, Adnan Chhatriwalla (St. Luke’s Mid America Heart Institute, Kansas City, MO), said a lot of physicians do not want to take cost into consideration when deciding on a treatment, that the goal instead is to be the patient’s advocate and do what’s best for them. Personally, though, he considers cost when making treatment decisions.

“I think it's no different than when patients come in to the office for blood pressure checks and they’re on antihypertensive medication—they want to be on the cheapest drug and it’s important to them,” said Chhatriwalla. “The same thing applies to, well, maybe not the stent cost itself because that probably doesn't really directly impact the patient, but to things like duration of antiplatelet therapy, [when] you know that patient is going to have to pay. And so I do take in the cost somewhat.”

In Canada, hospitals typically have contracts with single companies and receive discounted prices based on volume, said Sanjit Jolly, MD (McMaster University, Hamilton, Canada). Regarding payment, the hospitals are reimbursed a set amount for PCI and how they spend that money is their choice. “So, as you can see from a hospital perspective, buying a more expensive stent cuts into their bottom line,” he said. “They could potentially lose money on a PCI procedure versus having some extra to spend on other resources.”

When a new technology arrives—Health Canada approved Absorb BVS in mid-July—hospital product committees will advocate for a new device or technology if they believe it will improve clinical outcomes, said Jolly. “If, in the long term, the stent shows that it saves lives or improves outcomes, then people would be willing to spend that,” he said. “But if it’s not any better, then it gets more challenging to justify the cost to payers.”

A Widening Cast of Characters

Abbott is slowly rolling the Absorb stent out this summer, starting first with hospitals who participated in clinical trials testing the device. Absorb BVS is still so new that many of the high-profile interventional cardiology centers—Cleveland Clinic, Scripps Health, Johns Hopkins Hospital, and Massachusetts General Hospital, among others—have not yet had access to it in the commercial setting.

That’s expected to change very soon, though, with many of these hospitals eagerly awaiting their first shipment of Absorb stents. When physicians at the Cleveland Clinic and Scripps both talked with TCTMD earlier this month, they said they’re expecting to implant the stent in the coming days. For hospitals that have already implanted the device, the popular press is even paying attention, following up with physicians first in the city or state to implant the “disappearing” stent.

Abbott said they will require physicians to complete an online training program prior to receiving Absorb in their centers. In addition to the online training, the company is requesting physicians complete three cases with an Abbott proctor. The training, according to the company, is designed to “reinforce optimal stent implantation techniques, including proper vessel sizing, lesion preparation and postdilatation.”

Technique is important for mitigating some of the problems identified early on with this first-generation technology. Most physicians speaking with TCTMD over the past year have acknowledged that the device is trickier to implant than current-generation DES. Sorin Brener, MD (New York Methodist Hospital, Brooklyn, NY), called it clunky, saying it reminded him of the Cypher first-generation DES and is associated with a small increased risk of scaffold thrombosis. The safety concern was observed in the pivotal ABSORB III trial, which found the rate of definite/probable device thrombosis was numerically higher with Absorb, although the difference was not statistically significant compared with Xience (1.5% vs 0.7%; P = 0.13).

Since the publication of ABSORB III, several reports, including meta-analyses, registry data, and single-center experiences, have suggested there is an approximate two-fold higher risk of device thrombosis with Absorb compared with Xience. Other reports, including a patient-level, pooled meta-analysis conducted by ABSORB investigators, did not identify a significant increase in patient-oriented or device-oriented adverse events at 1 year when compared with Xience.

Gurpreet Sandhu, MD (Mayo Clinic, Rochester, MN), called the Absorb BVS a “very promising, early-stage technology,” adding, “Who wouldn’t want a stent that can treat a lesion and then disappear?” Like Brener, though, Sandhu said he and his colleagues have been aware of the stent’s limitations since it has been in development—thicker struts and reduced deliverability, among others—and that the technology is still in its infancy. So far, the clinical trials have been performed in best-case scenarios, such as patients with simple lesions and large vessels, where the stent has performed very well, but issues might arise in real-world patients.

“And there is still a higher incidence of stent thrombosis,” Sandhu told TCTMD. “The stent thrombosis rates have been almost double that of the current-generation drug-eluting stents. So in terms of what our impression is or what our thoughts are going forward, we are cautiously excited about the technology. It has lots of promise, but this is an early-generation technology and so we will be following the data and our own experiences very, very carefully."

European experiences with Absorb suggest that the potential risks can be mitigated with improved implantation techniques and by avoiding small vessels. Given the concerns about small vessels, the FDA approved Absorb for use in patients with a reference vessel diameter ≥ 2.5 mm and ≤ 3.75 mm.

“I think people shouldn't lose the fact in all this hoopla that this is indeed premium technology. This is an advance,” said Brener. “The current iteration may not be the best we can do, but that shouldn't dissuade us from using it or from continuing to develop it, refine it, and identify the proper use.”

Brenner envisions the stent’s biggest impact being in younger patients with very focal disease, in whom the eventual goal is the restoration of the artery to normal. “So I think people sometimes get frazzled by this report or that report, like the GHOST report from Europe,” he said. “We shouldn't lose track of the fact that this is a major advance in the technology. It's a phenomenal weapon for fighting coronary artery disease. It's just like everything else, it's just a stage. But we're not quite there yet."

A Totally Different Plot Line

Chhatriwalla said the best approach when thinking of the Absorb stent is to regard it as a “totally different technology” rather than as an improved DES. At present, the device’s drawbacks reinforce the need for the methodical roll-out and training protocol established by Abbott. Chhatriwalla said this will help ensure the device is implanted in the right patients and lesions and optimal results are achieved.

“I'll say that vessel preparation is more important when using these bioresorbable stents because they don't have the radial strength,” he said. With DES, even if the lesion is not fully open, physicians can implant and inflate a stent with good results because the current devices will open the artery. If the same approach is taken with the BVS, you’re not going to get a good outcome, he said. Physicians treating such lesions will need to dilate the vessel more or possibly perform atherectomy to reduce calcium burden in a heavily calcified lesion, Chhatriwalla advised.

Stephen Ellis, MD (Cleveland Clinic, OH), the lead investigator of ABSORB III, has completed the online training program created by Abbott, and said they are expecting to implant the first Absorb stent very soon. Like others, he described the device as a little bulkier than current-generation DES and emphasized the importance of preparing the lesion for the incoming stent.  

“You want to make sure that the artery will expand, so our predilatation strategy's somewhat more aggressive with this device,” he told TCTMD. “And to a certain extent [the same] regarding postdilatation. We certainly recommend postdilatation of at least moderate if not high pressure. We also suggest intravascular [imaging] if there's any question about the results. So yeah, I would say the whole procedure is somewhat different."

The Story So Far . . .

Hiram Bezerra, MD (UH Harrington Heart and Vascular Institute, Cleveland, OH), was among the first in the US Midwest to use Absorb commercially. When he spoke with TCTMD earlier this month, he had already implanted the device in five patients, including two with late stent failure with metallic DES. Those two patients, Bezerra told TCTMD, had previously been treated with multiple stents and had overlapping devices plus a large degree of neointimal hyperplasia proliferation. In both cases, he imaged the vessel with OCT and used coronary laser atherectomy to prepare the vessel for the Absorb stent.

“After OCT, we saw the previous stent was well expanded, although there was a lot of tissue inside,” said Bezerra. “After the laser, there was mild residual tissue, but we felt comfortable we could get good expansion of the BVS.”

He considers those first couple of cases—the patients with DES failure—as “symbolic” for the Absorb stent, noting that atherosclerosis is a lifelong disease and some patients will need to be treated again. As for the other three cases, Bezerra said they were “nothing special” de novo lesions that could have been treated with a metallic DES. Bezerra admits he is an enthusiast for the technology—which has been cultivated through being involved in the imaging core laboratory for the ABSORB studies—but says the stent, if it succeeds with good long-term results will disrupt the field of interventional cardiology.  

“I think data supports avoiding small vessels, meaning less than 2.5 mm by intravascular imaging, but other than that—and it’s a provocative way of thinking—the question is, why not use the BVS?” he said. “If you do a good job at baseline and invest the time in intravascular imaging, lesion preparation, and really get an excellent result, you can neutralize the first year concerns [about scaffold thrombosis].”

To TCTMD, Ellis said that given some of earlier questions raised, they will initially implant the stent in patients who met the criteria for ABSORB III, paying particular attention to vessel diameter and avoiding small vessels where the risk of scaffold thrombosis is highest. “I think, at least talking to my colleagues here, we'll be somewhat conservative about its use and really try to pick out the ideal patients with focal lesions and large vessels, [those] probably with a fairly long life span ahead of them,” he said. “[We’ll] get started with those patients and see how it goes."

In terms of estimating how many patients might be eligible for Absorb, Ellis noted the Cleveland Clinic is a tertiary referral center that largely treats patients with prior CABG or advanced disease, so it’s unlikely they’ll use the new stent in more than 10% of patients. Bezerra, on the other hand, estimated that as many as 60% to 70% could be candidates for Absorb.

. . . With More Still to Be Written

The allure of the Absorb stent, of course, is better long-term outcomes facilitated by the restoration of the occluded vessel to a relatively normal artery. Although the stent is not yet widely available, many have said they want to use it, citing the theoretical benefit of not leaving metal behind in the artery.

For Barry Uretsky, MD (University of Arkansas for Medical Sciences, Little Rock), the idea of the stent as a temporary repair that doesn’t leave behind anything is promising.

“I'm kind of at the far end of the spectrum, where I take care of patients with severe multivessel disease,” he told TCTMD. “One of the limiting factors for me is that sometimes I have patients with two and three layers of stents, which makes the vessels essentially noncompliant [and] more like metal tubes than real arteries. So if we are going to manage patients for a lifetime over 30 or 40 years, the concept of the stents resorbing over time so that when new lesions develop you’re starting over again relatively intact, nonmetal artery is exciting.”

As every physician interviewed admitted, this theoretical advantage and potential benefit needs to be proven, though. The ABSORB IV trial is enrolling 3,000 patients with coronary artery lesions to treatment with Absorb BVS and Xience. As part of the study protocol, investigators are combining patients from ABSORB III and IV to assess rates of target lesion failure (cardiac death, target vessel MI, or target lesion revascularization) between 1 and 5 years in the two study arms. The trial will include noninferiority and superiority analyses. 

“I think it’s going to take 3-, 4-, 5-year studies before we really know that it’s better not to leave metal behind in the artery as compared to a metal stent,” said Chhatriwalla. “So I think that unfortunately we are going to be waiting awhile."

Exactly where cost-efficacy lands in the years to come is a chapter for another day.

Importantly, Abbott is not alone in manufacturing a bioresorbable stent. In fact, the DESolve novolimus-eluting bioresorbable coronary scaffold (Elixir Medical Corporation) also has CE Mark approval in Europe, although the Absorb BVS has been more extensively tested and has significantly larger market penetration. In addition to Absorb and DESolve, there are numerous bioresorbable stents in development, with some in advanced testing. Such healthy competition would not only lead to better and better devices, but it is hoped that multiple stent companies competing for space on cath lab shelves would lessen the financial impact of this new technology.  

 

Michael H. Wilson, the 2016 recipient of the Jason Kahn Fellowship in Medical Journalism, contributed to the reporting of this story.