Fellows’ Corner: Bioabsorbable and Bioresorbable Stents of the Future - What, why, how, and when? | Ada C. Stefanescu Schmidt, Fellow-in-Training at the Massachusetts General Hospital in Boston, MA
CardioSource WorldNews Interventions | The last 18 months have brought us results of several trials of bioabsorbable and bioresorbable vascular scaffolds (BVS), technologies pioneered in the last decade to cover plaque and areas of endothelial injury, maintain vessel patency and avoid adverse remodeling during the vulnerable healing phase, and then be absorbed to reduce the potential for thrombogenicity of prosthetic material and technical limitations for future interventions arising from multiple layers of scaffold. The potential of the technology has garnered wide interest in the lay press, and patients are asking about its commercial availability with an increasing frequency. We will summarize the current data, use of the stents, and future directions of study, focusing on BVS.
Based on studies of coronary balloon angioplasty, vessel recoil and restenosis from neointimal hyperplasia are common within the first 6 months after the procedure; a scaffold to maintain patency in that time period was needed, and led to the introduction of bare-metal stents (BMS).1,2 Drug-eluting stents (DES), which release medications from a durable polymer coating on their metallic struts, were then designed to reduce neointimal hyperplasia and carry lower rates of restenosis than BMS. Inhibition of intimal growth and a persistent inflammatory response to the polymer coating of DES however were found to be associated with a low but persistent rate of late and very late stent thrombosis, leading to recommendations of longer dual antiplatelet therapy after DES than after BMS; newer generation DES carry a lower risk of stent thrombosis and a shorter duration of double antiplatelet therapy may be safe.3 Stents with a dissolving polymer coating were thus hypothesized to have lower stent thrombosis rates, and entered human trials in 2008. There is currently one bioabsorbable stent on the United States market, with a platinum-chromium scaffold covered with a poly(D,L-lactide-co-glycolide) polymer and everolimus on the abluminal aspect of the stent (Synergy, Boston Scientific, Natick, MA; approved by the FDA in Oct. 2015). The stent is drug-eluting for approximately 3 months, which is also the time frame of absorption of the polymer; the metallic scaffold remains. Taking a step further, bioresorbable vascular scaffolds (BVS) were then designed aiming to improve endothelial healing and reduce long-term restenosis risk; they are composed of a drug-eluting polymer scaffold with no underlying metallic struts. One BVS has received FDA approval this month (Absorb stent, Abbott Vascular; Abbott Park, IL),4 and both it and the novolimus-eluting DESolve stent (Elixir Medical, Sunnydale, CA) have CE mark for coronary intervention and are used in Europe. Both the Absorb and DESolve stents are constructed with a polyL-lactic acid backbone and everolimus coating, and are completely resorbed by 2 to 3 years on optical coherence tomography; the stented segments appeared endotheliazed,5 suggestive of vascular healing. In order to achieve comparable radial strength to current DES, BVS have thicker struts (150μm for the Absorb compared to 81–86μm for the Promus Element Plus DES and 74–81μm for the Synergy bioabsorbable stent6), and are also more fragile and prone to stent fracture during post-dilation. Lesion preparation appears to be especially important to reduce the risk of needing a high-pressure balloon post-dilatation and reduce the risk of stent recoil.7
The ASBORB III trial8 is the largest and most recent randomized trial of BVS to date. It evaluated the efficacy of an everolimus-eluting bioresorbable scaffold (Absorb; 1322 patients) compared to an everolimus-eluting stent (EES; 686 patients) in patients with stable or unstable angina. The study was designed for non-inferiority of the primary endpoint of target-lesion failure, a composite of cardiac death, target vessel myocardial infarction (MI), or ischemia-driven target-lesion revascularization at 1 year. The rate of the primary endpoint was 7.8% in the Absorb arm vs. 6.1% in the placebo group, meeting the test for non-inferiority (95% CI for rate difference of -0.5 to 3.9, p = 0.007). There was however an increase in subacute stent thrombosis in the Absorb arm (occurring between 24 hours and 30 days post-PCI, 12/1315 (0.9%) vs. 1/686 (0.1%) in Xience, p = 0.04) and a signal of higher rates of cardiac death (0.6% vs. 0.1%, p = 0.29), target-vessel MI (6.0% vs. 4.6%, p = 0.18) and target-lesion revascularization (3.0% vs. 2.5%, p = 0.5). The Absorb BVS was also tested in a smaller randomized trial in patients with STEMI,9 where it met the test for non-inferiority in a composite primary endpoint of invasive assessment of the target lesion at 6 months with a novel “healing score”, a composite of intraluminal mass, malapposed and/or uncovered struts. A large multicenter study of the GHOST-EU registry reported similar rates of target-lesion failure at 6 months (cumulative rate of 4.4% in 1731 patients for the composite of cardiac death, target vessel MI, clinically driven target vessel revascularization) with a persistent signal of moderately high rates of scaffold thrombosis (2.1% at 6 months);10 higher rates are seen in ostial lesions (15.4% target vessel failure and 4.9% scaffold thrombosis at one year).11 No significant differences in device-oriented composite outcome or stent thrombosis were however seen after propensity-matching to patients from the Xience V USA registry.12 A recent patient-level meta-analysis13 of the randomized trials of the Absorb BVS vs. Xience that had at least 1 year of follow-up (ABSORB II,5 ABSORB Japan,14 ABSORB China15 and ABSORB III8) did not find a significant difference between the Absorb BVS (n = 2164 patients) and Xience DES (n = 1225 patients) in target lesion failure (cardiac mortality, target vessel-related MI, ischemia-driven target lesion revascularization) at one year (RR 1.12, 95% CI 0.47-2.69, p = 0.17), but an increase in the incidence of target lesion failure in the first 30 days after PCI (RR 2.49, 95% CI 1.0-2.22, p = 0.051) and target vessel-related MI over the whole time period (5.1% vs. 3.3%, RR 1.42, 1.02-2.07, p = 0.04) were noted, with a trend towards higher incidence of stent thrombosis (1.3% vs. 0.6%, p = 0.08). The landmark trial to assess potential long-term benefits of the BVS is currently enrolling, with co-primary endpoints of recurrent angina at one year and a combined endpoint of target-lesion failure between 1 and 5 years (in which analysis the subjects from ABSORB III will be included); the early and medium-term safety of the scaffold will continue to be an question of interest as more experience increases with the delivery system and a more varied patient population.
Importantly, BVS have promising uses in specific sub-populations, including cardiac transplant recipients, patients with radiation-induced coronary disease, peripheral interventions, spontaneous coronary artery dissections, and congenital heart disease patients. Both cardiac allograft vasculopathy and radiation appear to cause constrictive remodeling of the coronaries, and both populations are generally young, tend to have simple lesions and face the need for re-intervention- characteristics which make them particularly well-suited for BVS; a randomized trial of the Absorb BVS is under way in patients post-cardiac transplant.16 The increased stent flexibility seen in BVS is of interest in peripheral interventions, in particular in segments with vessel deformation such as the superficial femoral artery and the popliteal artery behind the knee.17 A novel application for BVS is in the treatment of large vessel stenosis in infants and small children, particularly useful in view of the growth of the child and need for re-intervention. Successful use of BVS has been reported in branch pulmonary artery stenosis,18,19 Blalock-Taussig shunt thrombosis, coronary stenosis, and in coarctation of the aorta.20, 21
This innovation in the field of interventional cardiology holds promises in both prevalent coronary disease and niche populations in which it serves an unmet need, and further data is needed on its safety and risk-benefit profile.
Ada C. Stefanescu Schmidt is a Fellow-in-Training at the Massachusetts General Hospital in Boston, MA. She is doing outcomes research in interventional cardiology at the Brigham and Women’s Hospital, and is interested in adult congenital heart disease.
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- Administration USFaD. Absorb GT1™ Bioresorbable Vascular Scaffold (BVS) System - P150023. 2016.
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