A quantitative study of the effects of a dual layer coating drug-eluting stent on safety and efficacy

Abstract

A key strategy for increasing drug mass (DM) while maintaining good safety is to improve the drug release profile (RP). We designed a dual layer coating drug-eluting stent (DES) that exhibited smaller concentration gradients between the coating and the artery wall and significantly impacted the drug RP. However, a detailed understanding of the effects of the DES designed by our team on safety and efficacy is still lacking. The objective of this study was to provide a comprehensive multiscale computational framework that would allow us to probe the safety and efficacy of the DES we designed. This framework consisted of four coupled modules, namely (1) a mechanical stimuli module, simulating mechanical stimuli caused by percutaneous coronary intervention through a finite element analysis, (2) an inflammation module, simulating inflammation of vascular smooth muscle cells (VSMCs) induced by mechanical stimuli through an agent-based model (ABM), (3) a drug transport module, simulating drug transport through a continuum-based approach, and (4) a mitosis module, simulating VSMC mitosis through an ABM. Our results indicated that when the DM increased to two times the initial DM value, the DES we designed had higher safety and lower efficacy values than a conventional DES. When the DM increased to five times the initial DM value, the DES we designed had higher safety than a conventional DES, and negligible differences in efficacy compared with a conventional DES. In summary, the DES we designed exhibited a significant advantage in safety, but a slightly reduced efficacy compared with that of a conventional DES.