Second-generation everolimus-eluting intracoronary stents: a comprehensive review of the clinical evidence

Abstract

Percutaneous coronary intervention with implantation of second-generation drug-eluting stents (DES) has emerged as a mainstay for the treatment of obstructive coronary artery disease given its beneficial impact on clinical outcomes in these patients. Everolimus-eluting stents (EES) are one of the most frequently implanted second-generation DES; their use for the treatment of a wide range of patients including those with complex coronary lesions is supported by compelling evidence. Although newer stent platforms such as biodegradable polymer DES may lower local vessel inflammation, their efficacy and safety have not yet surpassed that of Xience stents. This article summarizes the properties of the Xience family of EES and the evidence supporting their use across diverse patient demographics and coronary lesion morphologies.

Plain language summary

Patients with coronary artery disease (CAD) often require treatment for symptoms caused by blockages in coronary arteries. In addition to medical therapy, available procedure options include either coronary artery bypass grafting, a major heart surgery or percutaneous coronary intervention (PCI) with stenting. PCI is a minimally invasive procedure where a metallic stent (a mesh made up of fine metallic network in a tube shape used to keep vessels open) is advanced over a wire through an artery to open the coronary artery blockage. Over the past few decades, improvements in procedure technique and stent material have made PCI a highly safe and efficacious procedure. A newer generation of stents, known as drug-eluting stents (DES), have been developed in which metallic struts are covered with a highly biocompatible polymer (a thin material coating over the metallic mesh)  that releases drugs at the blockage site to prevent local cell growth in the vessel wall. Among the second-generation DES, Xience everolimus-eluting stents (EES) have shown better outcomes compared with earlier generations of stents. Another version of DES with biodegradable polymer coating is emerging but their advantage over EES remains uncertain. Currently, Xience EES are one of the most commonly used stents to treat CAD. This manuscript covers an in-depth review of clinical evidence on the performance of Xience stents in a diverse range patient populations.

Tweetable abstract

Everolimus-eluting stents are one of the most frequently implanted medical devices for the treatment of a wide range of patients with complex coronary lesions. This article by Goel et al. summarizes the clinical evidence for the Xience family of second generation EES.

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@ridhimagoel547 @Drroxmehran @AlessSpirito @drbirgitvogel @DeborahKalkman

Executive summary

Overview of the market

• The field of percutaneous coronary intervention and stent devices has evolved significantly from bare-metal stents to durable polymer stents coated with antiproliferative agents. Currently, second-generation drug-eluting stents (DES) are the most frequently utilized stents in patients undergoing percutaneous coronary intervention.

• Xience stents are one of the most frequently used DES, with more than 15 million devices implanted globally by 2022, and form the benchmark to evaluate new stent technologies.

Device design

• Xience stents are characterized by 81-μm struts made from a cobalt-chromium alloy and covered with a durable polymer coated with everolimus as the neointimal antiproliferative agent.

• The Xience family of stents includes seven versions: Xience V, Nano, Prime, Xpedition, Sierra, Alpine and Skypoint.

• These stents are available in lengths ranging between 8 and 38 mm, and diameters from 2.25 to 5.0 mm.

Clinical evidence

• By 2022, Xience stents have been studied in more than 150 clinical studies worldwide. The 12 SPIRIT studies enrolling a total of 10,400 patients led to the regulatory approvals of Xience stents. Long-term follow-up data from post-approval registries have shown consistent benefits in unselected real-world populations.

• Clinical studies have demonstrated the efficacy and safety of Xience stents in treating a broad range of patients, including those with diabetes mellitus and women, and complex lesion morphologies such as left main disease, small vessels, long lesions and chronic total occlusion.

Emerging concepts

• Biodegradable polymer DES are theorized to lower local vessel inflammation compared with DP-DES; however, given the inconsistent results of randomized trials on the clinical advantage of this type of devices, second-generation DES with a durable or biodegradable polymer are considered both equivalent and recommended across different patient populations and clinical settings.

• Clinical trials have shown that after Xience stent implantation, shorter dual antiplatelet therapy (DAPT) regimens of 1–3 months followed by either aspirin or a P2Y₁₂-I monotherapy can be safely used to reduce bleeding events without significantly increasing ischemic events in most patients. However, in patients with acute coronary syndrome, potent P2Y₁₂ inhibitors should be preferred, since monotherapy with clopidogrel after a short period of DAPT may increase the risk of myocardial infarction compared with standard 12-month DAPT.

Regulatory status

• Xience stents have been approved by all major regulatory agencies for the treatment of obstructive coronary artery disease and are commercially available in several countries.

Keywords: :

• coronary artery disease
• drug-eluting stents
• dual antiplatelet therapy
• durable polymer everolimus-eluting stents
• percutaneous coronary intervention

Financial disclosure

A Spirito received a research grant from the Swiss National Science Foundation. R Mehran reports institutional research payments from Abbott, Abiomed, Alleviant Medical, Amgen, AM-Pharma, Arena, AstraZeneca, Atricure, Bayer, Biosensors, Biotronik, Boston Scientific, Bristol-Myers Squibb, CardiaWave, CeloNova, Chiesi, Concept Medical, CSL Behring, Cytosorbents, Daiichi Sankyo, Element Science, Faraday, Filterlex Medical, Humacyte, Idorsia Pharmaceuticals, Janssen, Mediasphere, Medtelligence, Medtronic, Novartis, OrbusNeich, Penumbra, PhaseBio, Philips, Pi-Cardia, PLx Pharma, Protembis, RenalPro, RM Global, Shockwave, Vivasure and Zoll; personal fees from Cine-Med Research, Ionis Pharmaceuticals, Novartis, Novo Nordisk, Vectura and WebMD; equity <1% in Applied Therapeutics, Elixir Medical, Stel, ControlRad (spouse); AMA (Scientific Advisory Board, JAMA Cardiology Associate Editor), ACC (BOT Member, SC Member CTR Program) and SCAI (Women in Innovations Committee Member; Faculty CRF (no fee). 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.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

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