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

Abstract

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.

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 residence in the arterial wall.

  • Thromboresistance might be important for reducing the mandatory duration of dual antiplatelet therapy and functional endothelialization might allow better long-term healing and prevent neoatherosclerosis.

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Fig. 1: Micro-CT images of drug-eluting stents.
Fig. 2: Inflammation in first-generation and newer-generation stents.
Fig. 3: Confocal microscopy images showing thrombogenicity of stents.
Fig. 4: Neointimal coverage of stents implanted in pig coronary arteries.
Fig. 5: Macrophage infiltration into stents implanted in rabbit iliac vessels.
Fig. 6: Endothelial barrier function for a bare-metal stent and a Synergy everolimus-eluting stent.

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S.T., A.S., S.K., L.G. and R.V. researched data for the article. S.T., A.S., M.K., A.C., S.K., L.G., H.M., E.H., K.H.P., R.F., R.V. and A.V.F. discussed the content of the article. S.T., R.V. and A.V.F. wrote the manuscript. S.T., H.J., A.S., A.C., H.M., D.C., M.E.R., F.D.K., A.G., R.V. and A.V.F. reviewed and edited the manuscript before submission.

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Correspondence to Aloke V. Finn.

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S.T. receives research grants from SUNRISE lab. A.C. receives research grants from University Hospital RWTH Aachen. R.V. and A.V.F. have received institutional research support from 480 Biomedical, 4C Medical, 4Tech, Abbott, Accumedical, Amgen, Bard, Biosensors, Boston Scientific, Cardiac Implants, Celonova, Claret Medical, Concept Medical, Cook, CSI, DuNing, Edwards LifeSciences, Emboline, Endotronix, Envision Scientific, Gateway, Leducq Foundation Grant (R01 HL141425), Lifetech, Limflo, MedAlliance, Medtronic, Mercator, Merill, Microport Medical, Microvention, Mitraalign, Mitra assist, NAMSA, Nanova, Neovasc, NIPRO, Novogate, Occulotech, OrbusNeich Medical, Phenox, Profusa, Protembis, Qool, Recor, Senseonics, Shockwave, Sinomed, Spectranetics, Surmodics, Symic, Vesper, W.L. Gore and Xeltis. R.V. has received honoraria from Abbott Vascular, Biosensors, Boston Scientific, Celonova, Cook Medical, Cordis, CSI, Lutonix Bard, Medtronic, OrbusNeich Medical, CeloNova, SINO Medical Technology, ReCore, Spectranetics, Terumo Corporation and W. L. Gore. R.V. is a consultant for Abbott Vascular, Boston Scientific, Celonova, Cook Medical, Cordis, CSI, Edwards Lifescience, Lutonix Bard, Medtronic, OrbusNeich Medical, ReCore, Sinomededical Technology, Spectranetics, Surmodics, Terumo Corporation, W. L. Gore and Xeltis. A.V.F. has received honoraria from Abbott Vascular, Biosensors, Boston Scientific, Celonova, Cook Medical, CSI, Lutonix Bard, Sinomed and Terumo Corporation. A.V.F. is a consultant for Amgen, Abbott Vascular, Boston Scientific, Celonova, Cook Medical, Lutonix Bard and Sinomed. The other authors declare no competing interests.

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Nature Reviews Cardiology thanks A. Kastrati, P. Serruys and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Torii, S., Jinnouchi, H., Sakamoto, A. et al. Drug-eluting coronary stents: insights from preclinical and pathology studies. Nat Rev Cardiol 17, 37–51 (2020). https://doi.org/10.1038/s41569-019-0234-x

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