March 19, 2008 (London, UK) - One-year results from the ABSORB bioabsorbable everolimus stent (BVS) trial, now published in the March 15, 2008 issue of the Lancet, demonstrate the feasibility of using Abbott's BVS device and the durability of its antirestenotic properties, at least over the first 12 months . But a mean loss in stent area over the follow-up period, reflecting acute stent recoil, nonuniform structural support, or dwindling stent strength related to bioabsorption, remains one of the major challenges ahead for the device, researchers say.
"There are many who think absorbable stents are the next great hope, but many do not," lead author Dr John Ormiston (Mercy Hospital, Auckland, New Zealand) told heartwire . "I think they are likely to be [the next great hope], but there are challenges to overcome. This paper tells us that a bioabsorbable [drug-eluting stent] DES--the BVS--can work in simple lesions. We need information from more complex lesions and in larger numbers of patients and from randomized trials."
In recent years, particularly given concerns about the risk of late stent thrombosis associated with permanent metal stents, interventionalists have predicted that bioabsorbable drug-eluting stents would be the wave of the future, eluting antirestenotic agents and providing the required scaffolding during the healing period, then dissolving away completely.
ABSORB at 12 months
As previously reported by heartwire , ABSORB enrolled 30 patients at four centers internationally. The results published this week represent one-year clinical follow-up, as well as angiographic, intravascular ultrasound (IVUS), and optical coherence tomography (OCT) results in smaller subsets within the overall group. In ABSORB, designed as a single-arm feasibility study, all patients received the investigational device.
As Ormiston and colleagues report, one patient had a non-Q-wave MI during the 12 months of follow-up. They explain that this patient had been admitted with chest pain and underwent target lesion revascularization (TLR) and received a paclitaxel-eluting stent, although this procedure did not actually meet the study definition of TLR because the angiographic assessment suggested the stenosis was less than 50% in diameter--below the prespecified cut-off for ischemia-driven TLR in the study. There were also no instances of stent thrombosis, the authors report.
Angiographic follow-up in 26 patients, as previously reported by heartwire , indicated that binary restenosis occurred in three patients (12%) and that the mean in-stent late loss was 0.44 mm at six months. This amount of late loss, they note, is similar to that reported for the Taxus paclitaxel-eluting stent (0.39 mm), higher than that seen in trials of the metallic everolimus-eluting stent (0.15 mm) but substantially lower than that of bare-metal stents (typically greater than 0.8 mm).
Keeping the vessel open
IVUS analyses pointed to a significant reduction in stent area (the amount of vessel propped open by the stent) and, in six patients, incomplete stent strut apposition--a phenomenon also seen on OCT in a subset of 13 patients. The reduction in stent area appeared to have occurred in a nonuniform fashion throughout the stent length, with less stent recoil occurring in areas with more stent struts, the authors note.
These observations have been taken into account in the design of the next-generation BVS, Ormiston told heartwire . "The next-generation Abbott BVS design will have more uniform scaffolding so that the vessel wall will be supported more uniformly and the drug applied more uniformly. It will also have more radial strength that will last longer," he explained. "This should reduce the small amount of late recoil seen in the trial. In addition, the stent will be very secure on the delivery balloon and have little chance of dislodgement."
While several companies are developing bioabsorbable stents, one of the outstanding questions remains just how quickly or slowly the stent should degrade. The rate of absorption has profound implications for stent efficacy, but also for long-term safety.
"As the stent is absorbed, its radial strength reduces and goes away; then some time elapses before the stent is completely absorbed," Ormiston noted. "In the ABSORB study at six months, there were profound changes in the struts as observed by OCT, indicating that absorption is well under way, but the stent had not been completely absorbed."
In preclinical studies, the BVS appeared to absorb completely within two to three years, but stent behavior may be very different in diseased human arteries, Ormiston told heartwire . "In patients, it seems to be absorbing faster than expected. There has been no increase in MACE by 12 months, and it would be surprising if there will be device-related MACE subsequently. Time will tell."
Better metal stents or disappearing stents?
In an accompanying editorial , Drs Carlo Di Mario (Royal Brompton Hospital, London, UK) and Giuseppe Ferrante (Catholic University of the Sacred Heart, Rome, Italy) ask whether there will indeed be a real advantage of bioabsorbable stents over permanent metal stents if, in fact, they take two to three years to dissolve; they point out that there are no solid data proving that the risk of stent thrombosis with metallic stents persists beyond three to four years. Increasingly, researchers studying the mechanisms of late stent thrombosis are concluding that the real culprit in stent thrombosis is the polymer and drug-release kinetics, not the stent itself. Some companies, as a result, are moving forward with metallic stents, but with bioerodable polymers.
"Will the progress of metallic stents with thin struts covered by a film of biodegradable polymer and less aggressive drugs be enough to eliminate late stent thrombosis?" the editorialists ask. "We doubt it. . . . Events as potentially deadly as stent thrombosis should ideally be eradicated; and radical alternatives to conventional stents, such as biodegradable stents, deserve to be the focus of research investment."
Ormiston, similarly, acknowledged that it's an "intriguing question" as to whether the late stent thrombosis problem will be solved by the stent disappearing altogether. "It is an important hope that if the strut disappears, there will be no potential for late stent thrombosis. However, late stent thrombosis may be more complex than an interplay of strut presence and endothelialization. I personally believe that a bioabsorbable stent is the way of the future if technical challenges can be overcome."
ABSORB investigators are moving ahead with a second cohort of 30 patients who will receive the next iteration of the BVS stent; enrollment will begin later in 2008, Ormiston said.
Ormiston declared having no conflicts of interest; two of the study coauthors are employees of Abbott, the study sponsor.
Ormiston J, Serruys PW, Regar E, et al. A bioabsorbable everolimus-eluting coronary stent system for patients with single de-novo coronary artery lesions (ABSORB): a prospective open-label trial. Lancet 2008; 371:899-907.
Di Mario C, Ferrante G. Biodegradable drug-eluting stents: promises and pitfalls. Lancet 2008; 371:873-874.
Heartwire from Medscape © 2008 Medscape
Cite this: Shelley Wood . ABSORBing the Details: 12-Month Results for Bioabsorbable, Everolimus-Eluting Stent - Medscape - Mar 19, 2008.