Review
The Evolution of Coronary Stents: A Brief Review

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Abstract

Percutaneous coronary intervention is the most prevalent method for coronary artery revascularization. Initial interventions using balloon angioplasty had limited efficacy because coronary dissections, arterial recoil, and neointimal formation led to high rates of abrupt vessel closure and clinical restenosis. With the introduction of coronary stents, vascular dissections were stabilized and arterial recoil was eliminated, but neointimal accumulation remained problematic, resulting in the development of in-stent restenosis (ISR) in 20%-30% of cases. Drug-eluting stents (DESs) were developed to release antiproliferative agents at the site of arterial injury to attenuate neointimal formation. Although DESs have incrementally improved outcomes after percutaneous coronary intervention, delayed re-endothelialization and stent thrombosis remain important challenges. Herein we review the pathophysiology of ISR, stent thrombosis, and briefly summarize the clinical evidence behind first- and second-generation DESs. Moreover, we discuss advancements in our understanding of the pathogenesis of ISR and potential novel therapeutic strategies to improve clinical outcomes.

Résumé

L’intervention coronarienne percutanée est la méthode de revascularisation coronarienne la plus répandue. Les interventions initiales au moyen de l’angioplastie par cathéter á ballonnet avaient limité l’efficacité puisque les dissections de l’artère coronaire, le recul de la paroi artérielle et la formation néointimale ont mené à des taux élevés de fermeture abrupte d’un vaisseau et de resténose clinique. Par l’introduction d’endoprothèses coronaires, les dissections vasculaires étaient stabilisées et le recul de la paroi artérielle était éliminé, cependant l’accumulation néointimale demeurait problématique, entraînant le développement de la resténose intrastent (RIS) dans 20 % à 30 % des cas. Les endoprothèses médicamentées (EM) étaient conçues pour libérer les agents antiprolifératifs au site de la lésion artérielle afin d’atténuer la formation néointimale. Bien que les EM aient progressivement amélioré les résultats après l’intervention coronarienne percutanée, le retard de réendothélialisation et la thrombose d’endoprothèse restent des enjeux importants. Ici, nous passons en revue la physiopathologie de la RIS, la thrombose d’endoprothèse, et nous résumons brièvement les données cliniques qui sous-tendent l’utilisation des EM de première et de deuxième génération. De plus, nous discutons des progrès dans notre compréhension de la pathogenèse de la RIS et des nouvelles stratégies thérapeutiques potentielles pour améliorer les résultats cliniques.

Section snippets

Neointimal formation and ISR

The mechanisms underlying ISR after PCI remain incompletely understood. Indeed, the accepted pathogenesis of ISR is in flux as numerous animal models are used to attempt to mimic and explain the mechanisms leading to restenosis. These models and their implications for therapeutic intervention have recently been reviewed.5 The most widely accepted model is an adaptation of the “response-to-injury” model proposed by Ross in 1976, whereby the mechanical disruption of the endothelial lining by PCI

First-generation DESs

Although revolutionary at the time of their development, first-generation DESs are considered rudimentary by today's standards. They are comprised of a metallic stent platform (typically stainless steel) and coated with a polymer that elutes antiproliferative and/or anti-inflammatory therapeutic agents (ie, sirolimus or paclitaxel).

Novel Approaches to Stent Development

Although current DES technology focuses on mitigating ISR formation predominately by antiproliferative mechanisms, other novel approaches are presently being studied. Based on our expanding understanding of the pathophysiology of neointimal formation and ST, elution agents with diverse mechanisms of action are being developed.

Conclusions

The advent of DESs has undoubtedly improved outcomes in patients undergoing PCI. Although first-generation DESs advanced our treatment of obstructive coronary disease, ISR and ST presented important limitations. Second-generation stents have refined the struts, polymers, and drugs eluted, thereby improving early and late outcomes (Supplemental Fig. S1). Nonetheless, as our understanding of the pathophysiology behind these processes continues to evolve, so too will our therapeutic approaches.

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    These authors contributed equally to this work.

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