Drug-eluting stent safety: findings from preclinical studies

Abstract

After pivotal clinical trials, drug-eluting stents (DES) are now considered the standard of care for the management of acute coronary syndrome. However, late stent thrombosis has emerged as a major concern. Preclinical testing is an important regulatory process that determines the safety and efficacy of devices prior to human clinical trials. Histopathologic analysis following placement of DES has typically been performed in porcine coronary artery models to ensure safety in these devices. The recently issued consensus report from the US FDA, for the approval of DES recommends the use of the porcine model for the safety assessment of these devices in the vascular bed for which they are intended. Other models are also recommended, as vascular responses to stents are much slower in man than in animals, and no animal truly elicits the response seen in humans. The rabbit iliac artery can provide further data, especially regarding endothelialization, which is slower in the rabbit model than in the porcine model. Furthermore, inflammation is not as extensive in the rabbit and may thus be a closer model of humans than the porcine models. The FDA recognizes that it may be more appropriate to test these devices in atherosclerosis. The choice of animal model may mask the serious drawbacks of the devices; therefore, we suggest the use of both models to understand the healing following DES implantation, with emphasis on endothelialization, inflammation and neointimal formation and, whenever possible, to complement the observations in the environment of atherosclerosis.

Keywords::

• drug-eluting stent
• porcine model
• preclinical study
• rabbit model

Financial & competing interests disclosure

Renu Virmani receives company-sponsored research support from: Medtronic AVE; Abbott Vascular; Conor Medsystems; OrbusNeich; Terumo Corporation; Cordis Corporation; BioSensors International; Prescient Medical; Biotronik; and Alchimedics. He is also a Consultant for: Medtronic AVE; Abbott Vascular; Prescient Medical; and Biotronik.

Leslie Coleman is an employee of Abbott Vascular, Santa Clara, CA, USA.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.