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Bioabsorbable Scaffolds: Beyond the Vanishing Act
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PCI with bioabsorbable vascular scaffolds has created interest due to the temporary need for mechanical support for the healing artery, and the realization that beyond the first few months, there are potential disadvantages of a permanent metallic prosthesis.
There are several possible advantages of this novel technology. One, there is the potential to reduce the occurrence of stent thrombosis, in particular late and very late stent thrombosis. Once the antiproliferative drug and the temporary scaffold disappear, the possibility of thrombotic events in the site of PCI is considerably reduced.
Another advantage is in the restoration of endothelial function. Once the “rigid” scaffold structure is removed, the shear stress is restored, favoring a late increase in the vessel lumen. Furthermore, the full patency of the “jailed” side branches might be recovered.
Alexandre Abizaid
J. Ribamar Costa Jr.
There also is potential benefit in the pediatric setting because bioabsorbable scaffolds allow vessel growth and do not need eventual surgical removal. Added to which, there is the possibility of vessel assessment with non-invasive imaging modalities such as coronary CT or MRI. The current technology of metallic stents results in excessive artifacts on CT angiography, which precludes a definite noninvasive assessment of the stented segment. The absorbable scaffolds allow from day 1 a clear visualization of the entire coronary tree.
Further, there is the possibility of performing additional revascularization therapies in the treated segments. A current complaint is that the use of a “full metal jacket” to treat diffuse coronary disease might preclude CABG (or even repeat PCI) in cases of future failure of PCI. Since the bioabsorbable scaffold will be absorbed, in case of disease progression, the surgeon would still have coronary segments to perform the graft anastomosis.
The efforts to develop a fully degradable scaffold started about 20 years ago with the pioneering work of Willem J. van der Giessen, MD, PhD, A. Michael Lincoff, MD, and Tohru Yamawaki, MD. Despite the relative success in animal models, the initial prototypes resulted in excessive local inflammatory reaction, recoil and restenosis.
Currently, there are more than 10 different bioabsorbable vascular scaffold prototypes being tested in the preclinical scenario. Among the programs that reached clinical evaluation, four have drug-elution and have already delivered initial results in humans. The following is a brief review of those four.
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Figure 1. Panel A: Long lesion in the mid-RCA. Panels B and C: Deployment of two Absorb bioresorbable PLLA-based scaffolds (3 mm x 18 mm) with overlapping. Panel D: Acute result assessed with IVUS and optical coherence tomography. Panel E: One-month CT angiography showing stent patency with no artifact (except for the markers at the edges).
Images: Alexandre Abizaid, MD, and J. Ribamar Costa Jr., MD, PhD
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Absorb
The Abbott Bioresorbable Vascular Scaffold (BVS) program is by far the one with more patients enrolled and longer clinical follow-up (up to 5 years). This scaffold has a bioabsorbable polymer backbone of PLLA with a polymer coating (poly-D,L-lactide) that contains and controls the everolimus in a similar dose as the Xience V/Prime (Abbott). The first-in-man evaluation of this device in the ABSORB cohort A trial (n=30) showed a late lumen loss of 0.43 mm mainly at the expense of important scaffold recoil (roughly 12%).
Modifications in the BVS design with the addition of links, which resulted in an appearance similar to the original Multi-link stent, were done and the new version tested in the ABSORB cohort B trial (n=101). At 6 months, there was a significant improvement in late loss (0.19 mm) with barely any recoil (roughly 5%). Of note, from 6 to 24 months there was stability in the late loss and, more importantly, an expressive lumen enlargement due to scaffold bioresorption and plaque reduction behind its struts (Patrick W. Serruys, unpublished data).
This device is currently being evaluated in a larger, multicenter, single-arm registry (ABSORB extend trial) and a randomized trial (ABSORB II trial) vs. the metallic Xience Prime DES. The current challenge is to expand the indications of this technology to more challenging scenarios. Figure 1 shows an example of a patient treated in our institution as part of the Extend trial.
DESolve
The DESolve Bioresorbable Coronary Scaffold (Elixir Medical) is a PLLA-based scaffold coated with a bioresorbable polylactide-based polymer and the drug myolimus, a macrocyclic lactone mTOR inhibitor (drug dose is 3 mcg per mm of scaffold length). The DESolve system differentiates itself from previously studied bioresorbable scaffolds with several unique characteristics, each of which addresses an essential need not adequately met by other bioresorbable scaffolds or stents. These features include: bioresorption between 1 and 2 years while maintaining adequate support of the vessel wall; the elimination of chronic recoil; the ability to expand the scaffold without strut fracture; and availability in a wide range of sizes and lengths.
The initial in-human evaluation of this device was the DESolve first-in-man trial (n=15), which showed an effective neointimal hyperplasia suppression (late loss, 0.19 mm). Notably, instead of chronic recoil, IVUS and optical coherence tomography evaluation demonstrated a scaffold enlargement from baseline to midterm follow-up with virtually no strut incompletely apposed at 6 months (0.1%; source: Stefan Verheye, oral communication, EuroPCR 2012, Paris). Currently ongoing, the DESolve NX trial (n=120) is testing a new version of this scaffold with novolimus instead of myolimus. The device is available in three different diameters (3 mm, 3.25 mm and 3.5 mm) and two lengths (14 mm and 18 mm).
Figure 2 illustrates a case enrolled at our institution in the DESolve NX trial. The scaffold conformability is noteworthy.
Figure 2. Implant of a DESolve bioresorbable PLLA-based coronary scaffold in a very angulated proximal left anterior descending artery (LAD; left panel). As measured by the angulation of the artery, the presence of the scaffold just slightly modified the vessel anatomy (right panel), which might positively preserve the sheer stress and vessel physiology.
Absorbable Metal Stent
Contrary to the two previous programs, which developed bioabsorbable scaffolds based on polymeric material, the Absorbable Metal Stent (Biotronik) uses a magnesium alloy. The first-in-man evaluation of this technology in the PROGRESS trial (n=63) used a non-eluted version with very rapid absorption (2 months). As a result, at 4 months, late loss was 1.08 mm, mostly due to chronic scaffold recoil (roughly 53%) with unacceptable TLR rate of 23%.
Refinements in the scaffold design and absorption as well as incorporation of paclitaxel to the system resulted in better angiographic and clinical outcomes (BIOSOLVE I trial; n=46 patients). At 6 months, late loss was 0.64 mm, and the rate of target lesion revascularization was only 4.3%.
Currently, the company is working on the third version of this device with sirolimus elution.
ReZolve
REVA Medical has developed a unique and proprietary iodinated poly (DTE carbonate) material to serve as the base polymer for the device. The formulation of this material provides ReZolve with the ability to adjust the degradation profile to fit the desired application. The REVA scaffold is specifically engineered to not only maintain at least 75% of its initial mechanical strength to support the vessel through the most critical 3-month healing and remodeling phase, but also to no longer constrain the vessel and allow for the potential of expansive remodeling after 6 to 12 months.
Unlike traditional deformable metal stent designs, the REVA slide and lock design deploys by sliding open and locking into place, which completely eliminates the need to deform the device, making it ideally suited to use with polymers, which are inherently not as amenable to deformation as metals. Also, due to its material properties, the ReZolve scaffold has overcome a current major limitation of most biodegradable scaffolds: lack of radiopacity. Due to its backbone poly (DTE carbonate) matrix, which has a higher mass, this system has an enhanced X-ray visibility, superior to most of the metallic stents on the market (Figure 3). Although the acute results with the first generation of this device — without drug-elution — were very promising with high rates of procedural success, a higher than anticipated TLR rate occurred between 4 and 6 months after implantation.
Figure 3. Implant of a ReZolve poly (DTE carbonate)-based coronary scaffold in a mid-portion of a LAD (left panel). As noticed in the right panel, the scaffold has enhanced visibility due to the DTE carbonate properties.
To overcome this limitation, slight modifications on the device to improve its performance under load were made. The optimized polymer has been fully integrated with the next-generation slide and lock design and combined with delivery of sirolimus. The first-in-man assessment of this new generation of the REVA scaffold is currently ongoing in different sites in Europe and Brazil.
Conclusion
There is no doubt about the effectiveness of the current generation of metallic drug-eluting stents in preventing restenosis. However, concerns regarding the safety of these devices, as well as the durability of the anti-proliferative effect (late catch-up), have prompted the search for novel technologies.
We are living in the era of the vascular restoring therapy with the advent of bioabsorbable vascular scaffolds. The concept of a transitory vascular support, which mimics the initial effects of a metallic stent but “disappears” over the subsequent months, seems not only very attractive but also feasible according to preliminary evaluations. The current challenges of this new revolution in interventional cardiology comprise the expansion of their indication to more cumbersome scenarios and the long-term in vivo demonstration of their theoretical benefits.
Disclosure: Abizaid and Costa report no relevant financial disclosures.