Bioerodable Scaffolds: A "Disappearing Act"?

 

Presented at the 15th Biennial International Andreas Gruentzig Society Meeting, February 3-7, 2019

Program Agenda               Faculty Disclosures              Vendor Acknowledgment


10.1 / IAGS 2019
Session 10: Coronary Session 3
Bioerodable Scaffolds: A "Disappearing Act"?
Problem Presenter: J. Dawn Abbott, MD

 

Statement of the problem

Thin-strut metal alloy drug eluting stents (DES) with either biocompatible durable or bioresorbable polymers are the current standard of care in percutaneous coronary intervention (PCI). At 5 years, current generation zotarolimus and everolimus eluting stents both have remarkably low rates of clinically driven restenosis and stent thrombosis. Bioerodable or bioresorbable scaffolds (BRS), however, have potential advantages over durable metal platforms, including earlier and more complete restoration of coronary endothelial and vasomotor function, positive vascular remodeling, ability for reintervention including bypass of the coronary segment, and designs that have potential novel options for antiproliferative drug elution.

The first generation of BRS had several limitations, but early studies showed favorable safety and efficacy profiles, and several received CE mark in Europe. The Absorb BRS, which consisted of a 150-μm-thick bioresorbable poly(l -lactide) (PLLA) scaffold with a 7-μm thick bioresorbable poly(d,l -lactide) coating, and eluted everolimus, was FDA approved in 2016. Issues with first generation PLLA BRS, including Absorb, were lack of radio-opacity and thick struts which were necessary to achieve radial strength due to the tensile modulus of the material. These devices required cold storage, were difficult to deliver, had limited expansion capability, and were prone to fracture. These issues likely contributed to the slow uptake in the US. When large randomized trials reached three-year follow up, BRS were found to be associated with higher rates of adverse outcomes including target lesion failure and device thrombosis compared to metal alloy EES. In September 2017, there was a worldwide halt of sales of Absorb BRS. In Europe, the use of all remaining CE mark devices has been discouraged outside of clinical trials. 

 

Gaps in knowledge

Strut fracture and luminal protrusion are postulated to be factors responsible for late adverse events. The process of reabsorption of struts not in contact with the endothelium is altered and embolization into the distal vessel can occur. Additional mechanisms of late BRS failure are unclear but may be related to the vessel remodeling. While expansive remodeling is favorable with respect to an increase in luminal gain, the process could potentially be detrimental over time. DES failure includes stent thrombosis, neointimal hyperplasia and neoatherosclerosis. Whether BRS can reduce the incidence of neointimal hyperplasia through a more functional endothelium is unknown. The fundamental gaps in the field of coronary BRS include determining the optimal time course for absorption, ideal BRS materials including polymers, metals (magnesium), and most recently iron-based scaffolds, bioresorbable polymer and drug dosing, and the optimal adjunctive pharmacology such as dual antiplatelet therapy. 

 

Possible solutions and future directions

Several improvements to PLLA BRS are already in development. With advances in polymer science, and ability to manipulate PLLA molecules by stretching, warming, and cooling, scaffolds with thinner struts (~100 μm) that have greater capacity for full expansion with less risk of fracture, are in preclinical and early human trials. New technology will allow BRS to be constructed in layers rather than by extrusion which leads to novel designs of drug elution. Non-polymer materials are emerging, including a thin strut (~70 μm) iron based, PDLLA coated SES-eluting BRS that is in preclinical trials. This BRS reabsorbs through corrosion and dissolution into hemosiderin. The possibility to reduce thrombogenicity through inherent properties of metals and bioresorbable polymers also exists. Outside of BRS design, ideal patients and lesions need to be characterized, and vascular response to BRS should be defined over time by intracoronary imaging with optical coherence tomography. Lastly, in order to reduce ischemic events in BRS patients there needs to be a focus on reducing disease progression with high dose statins, and in specific high-risk subsets with alirocumab. While the removal of the first generation PLLA BRS from the market was a setback, there certainly remains momentum in the field that will ultimately yield a commercially available device in future years.