Abbott Laboratories Inc. ’s Absorb everolimus-eluting bioresorbable vascular scaffold(BVS) remains on track for a late-2015 PMA submission based on data showing the novel device performed at least as well as the company’s Xience everolimus-eluting metal stent at the one-year follow-up of the first randomized controlled trial for the dissolving coronary stent.

One-year results from 501 patients in the ABSORB II were presented at the Transcatheter Cardiovascular Therapeutics conference in Washington, D.C. on Sept. 14 by principal investigator Patrick Serruys, of the Erasmus University Hospital, Rotterdam, the Netherlands. The results were simultaneously published in The Lancet.

Unlike traditional metal stents, Absorb BVS is made of polylactide and dissolves into the vessel wall over time. Despite widespread dissemination of the device outside the U.S. since September 2012, ABSORB II is the first rigorous comparison with an everolimus-eluting metallic stent, Serruys explained. (See Also see "Abbott’s Bioresorbable Stent Shows Durable Results In ABSORB Trial" - Medtech Insight, 25 March, 2013.)

"We're really redefining coronary or vascular physiology with this technology,” Charles Simonton, Chief Medical Officer of Abbott’s vascular division told “The Gray Sheet” in an interview. “Of course we want to see the clinical outcomes, but [ABSORB II] was designed to look, at three years, at the function of the vessel itself, whether the device resorbs and you look at it head-to-head versus a metal cage. Once the vessel is set free, [as Absorb BVS disappears] then you see vasomotion, which means that the vessel is responding to the drugs and physiologic stimuli, which you want. The patient would want to have that vascular function.”

The trial enrolled patients with evidence of myocardial ischemia and one or two de-novo native lesions in different epicardial vessels. They were randomized in a two-to-one ratio to Absorb BVS or Xience. In addition to traditional percutaneous coronary intervention outcome measures, the trial is also comparing angina (chest pain) symptoms, change in lumen diameter and differences in vasomotion – ability of the vessel to expand and contract – of the treated vessels after three years.

Although the trial is designed around three-year endpoints, Abbott and the researchers elected to announce interim one-year data because, “along the way, the clinical community thought it was really important to see the big clinical events like death, MI, restenosis, and thrombosis and those sorts of things.” Simonton said.

At one year, the cumulative rates of first new or worsening angina from adverse event reporting were 22 percent in the Absorb BVS group versus 30 percent Xience group, a statistically significant difference. Measures of performance during maximum exercise and angina status by the Seattle Angina Questionnaire were similar for the two groups.

“The decrease in the cumulative rate of angina for bioresorbable scaffold was directionally consistent with the lower reported rates of nitrate use and all revascularizations,” Serruys et al. observe in The Lancet. “This observation is so far unexplained and merits additional research, although return of vasomotion, reduction of compliance mismatch, and improved conformability of the bioresorbable scaffold have been reported in previous studies.”

Serruys and Simonton both noted that Absorb matched the performance of Xience even though Xience performed extremely well in the trial.

The one-year composite of device-related adverse events was similar between the Absorb BVS and Xience groups, at 5 percent and 3 percent, respectively. The struts of the Absorb BVS are thicker than Xience’s struts, which could potentially cause more damage to the vessel wall during implant, but the ABBOTT II researcher’s comprehensive analysis of three sets of myocardial biomarkers did not find substantial difference of myonecrosis – muscle cell death – between the Absorb BVS and Xience groups. There were slightly more peri-procedural myocardial infarctions in the Absorb BVS group than the Xience group (3.9 percent versus 1.2 percent) but the difference was not statistically significant, Serruys reported.

Simonton predicts, "Over the next year or two, having seen the literature on what's happening long-term with metallic stents, there's going to be an increasing desire to for physicians to use the resorbable scaffold, even a first generation device.” Although the first-generation scaffold “might be a little more difficult to deliver than a thin-strutted metallic stent right now,” he said, “it’s worth an extra 10 or 15 minutes on a case to get a slightly less deliverable scaffold if you can give the patient the benefit over the next five or ten years they're going to be living.”

Five-Year Magic?

Also at TCT, on Sept. 13, Bernard De Bruyne of the OLV Hospital, Aalst, Belgium, presented five-year follow-up results from 24 patients in the single-arm ABSORB Cohort B trial.

Optical coherence (OCT) tomography imaging showed the Absorb scaffold completely resorbed by five years, and while most metallic stents cause “late lumen loss” – contraction of the open space within the stented vessel segment – in ABSORB Cohort B, angiography showed growth in the lumen diameter of vessels treated with Absorb BVS. De Bruyne said, the mechanism of this reduction in late loss could be due to expansive remodeling, late-lumen enlargement, or vessel wall-thinning and should be further explored with intravascular ultrasound and OCT.

Also, all of the patients to reach the five-year follow-up on ABSORB Cohort B demonstrated some degree of vasomotion in the stented segment in response to nitrates, whereas previous research has shown no vasomotion in segments with a metallic stent when tested with nitrates, De Bruyne said.

“The magic [of Absorb BVS] appears really after one year,” Simonton explained. “When you get to five years, when what you're seeing is, instead of the continued encroachment of the lumen that you get with a metallic stent, the [ Absorb BVS] scaffold itself loses structural restriction on the arteries as early as one year and is completely absorbed by three years.

“By five years, he noted, “the lumen can actually enlarge, which is a good thing, because then the vessel can defend against any new deposits of plaque and become much lower risk for future events for patients.”

ABSORB III and ABSORB IV

Abbott is currently sponsoring the ABSORB III randomized control trial in the U.S. to support FDA approval of Absorb BVS. The trial is randomizing over 2,000 patients to either Absorb or Xience and the primary endpoint is non-inferiority of target lesion failure at one-year. Target lesion failure is a composite of cardiac death, myocardial infarction attributable to the target vessel, or ischemia-driven target lesion revascularization. Simonton said ABSORB III finished enrolling patients in March and the company hopes to complete the PMA submission and publicly present data from the trial in the second half of 2015.

"Patients and physicians already understand intuitively that not having a permanent implant is a good thing. So once the ABSORB III [data] comes out with over 2,000, patients totally powered for clinical outcomes and proves safety and effectiveness at one year, I think you're going to see a really broad desire to adopt this technology widely,” Simonton said. “It's pretty intuitive that people don't want to have permanent implants and there's all kinds of data that, year over year, both bare metal stents and drug -eluting stents are associated with continued [adverse] events.”

He cited past research showing that the long-term adverse event rate related to permanent metal stent implants is between three and five percent per year. By those figures, since 80 percent of patients implanted with stents live at least another 10 years, as many as half of all stented patients will have some kind of adverse event following stenting.

On Sept. 15, Abbott announced the launch of the ABSORB IV trial, comparing Absorb BVS to Xience in about 3,000 patients at 140 sites. It will be the first randomized coronary stent trial to prospectively measure angina as a primary endpoint at one year, according to the company. The co-primary endpoint is target lesion failure, compared at one year and at five years follow-up.

Simonton said the company is also hopes to continue to refine the Absorb design to make the scaffold struts thinner so the device is easier to deliver. "We're excited about what we can do with this [polylactide] material and how we're going to get the next generation out to keep the leading spot in this field,” he said.

Other companies developing bioresorbable stents/scaffolds include Amaranth Medical Inc, Arterial Remodeling Technologies, Biotronik SE & Co. KG, Elixir Medical Corp., Kyoto Medical, Lifetech Scientific (Shenzhen) Co. Ltd., Huann, Medtronic PLC, OrbusNeich, REVA Medical Inc., S3V, Sahajanand Medical Technologies Pvt. Ltd., Xenogenics Corp., and Zorion Medical. (See Also see "Reinvigorating The Coronary Stent Market: Can Bioresorbable Scaffolds Do The Job?" - In Vivo, 25 July, 2013..)

The Case For Disappearing Stents: More Positive Data For Abbott’s Absorb BVS

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