Drug-eluting coronary stents: insights from preclinical and pathology studies

Implantation of drug-eluting stents (DES) is the dominant treatment strategy for patients with symptomatic coronary artery disease. However, the first-generation DES had substantial drawbacks, including delayed healing, local hypersensitivity reactions and neoatherosclerosis, which all led to a steady increase in major adverse cardiovascular events over time. Subsequently, newer-generation DES were introduced with thinner struts, different scaffold designs (to improve deliverability while maintaining radial strength), different durable and biodegradable polymers — and in some cases no polymer (to improve vascular biocompatibility) — and new antiproliferative drug types and doses. Currently, >30 different DES are commercially available in Europe, with fewer available in the USA but with many new entrants coming onto the US market in the next few years. Never before have cardiologists been faced with so many choices of stent, each with its own unique design. In this Review, we detail preclinical and pathology studies for each stent design, examining thromboresistance, speed of neointimal coverage and completeness of healing, including endothelialization. We conclude by discussing how these design characteristics might affect the potential for shortening the minimum duration of dual antiplatelet therapy needed after coronary intervention. This Review outlines the drawbacks and lessons learned from first-generation drug-eluting stents, and then discusses design features and preclinical, pathology and clinical data from newer-generation devices. The authors focus on how evolution in stent design has improved biomaterial–blood interactions and vascular healing. Key points Implantation of drug-eluting stents (DES) is the main treatment strategy for patients with coronary artery disease. Stent design, stent material, strut thickness and vessel-wall coverage all influence clinical outcomes, and thin-strut DES are the standard. Durable polymers, particularly fluoropolymers, are protective against thrombogenicity in the acute phase after stent implantation. Endothelial barrier dysfunction after DES implantation is caused by mechanistic target of rapamycin inhibitors and might have an important role in the pathogenesis of neoatherosclerosis. In experimental animal models, abluminally coated biodegradable-polymer DES and polymer-free DES allow earlier healing and faster return of endothelial barrier function than durable-polymer DES, owing to curtailed duration of drug