Dr Nick West, Consultant Cardiologist, Papworth Hospital, Cambridge, UK

Introduction

Since the widespread use of drug-eluting stents (DES), industry has provided interventional cardiologists with a variety of refinements – new drugs, new stent designs, new polymers and novel methods of delivering drug or altering release kinetics. Many (but not all) of these modifications have provided measurable, albeit small, improvements in performance and patient outcomes, with the result that currently-available DES provide single-figure rates of target vessel failure with an excellent safety profile at one-year follow-up. So why do we need a new stent material?

What’s wrong with current stent materials and construction?

The ideal metallic coronary stent should possess corrosion-resistance, biocompatibility, high radial strength and enough radio-opacity to facilitate visualisation under fluoroscopy as well as being non-ferromagnetic1. Historically, the majority of stents have been manufactured from surgical grade (316L) stainless steel, which fulfils most of these criteria but has limited radio-opacity unless stent struts are thick or coated with other metals (both of which have been shown to increase rates of restenosis)2 3, and crucially may not be as biocompatible as previously thought owing to elution of trace elements after implantation4. The advent of cobalt chromium (CoCr) alloys (L605 (Vision, Abbott Vascular), MP35N (Driver, Medtronic)) allowed for a thinner-strut stent construction from biocompatible compounds that have comparable strength and reasonable radio-opacity 5 6. The stent platforms made from these alloys have proved to be highly deliverable due to enhanced flexibility, exhibit low restenosis rates in their bare-metal configurations, but have sacrificed radial strength and resistance to elastic recoil to some degree due to their thin-strut design.

PtCr alloy and the Element stent

Platinum-Chromium (PtCr) is the first alloy developed specifically for coronary stent manufacture; platinum has been used in a variety of implantable medical devices over the last 20 years and has proved to be highly biocompatible due to its chemical stability. Addition of platinum to a stainless steel base enhances the strength of the compound allowing the potential for stronger struts of comparable thinness to those made from CoCr alloys, with improved radio-opacity 7 (Table 1). The PtCr alloy was developed specifically by Boston Scientific for the novel Element stent design (Figure 1) – a dimensionally uniform pattern of serpentine segments with two offset connectors that reverse directions for alternate rows, providing a design partway between cellular and modular that is highly deliverable and conformable, and provides compression/recoil resistance comparable to that of 316L stainless steel stents.

The Element platform has been optimised in its deployed conformation to allow as uniform drug-delivery to the vessel wall as possible; the Promus Element was released in the UK in November 2009, with the Taxus version available later this year, followed by the bare-metal iteration in due course. For each of the drug-eluting versions, the drug concentration and polymer will be identical, respectively, to the extensively-trialled and established Promus/Xience V and Taxus Liberte stent designs.

The Element stent program

Prior to launch, the Element trial program was initiated, from which the first results will be presented at the ACC in March this year. For each of the drug-eluting versions of the Element stent, there already exists a large body of registry and randomised controlled trial (RCT) data relating to its ‘parent’ stents, which will be supplemented by new data comparing these platforms to their Element counterparts. The Platinum trial, involving 1532 patients in 160 centres, is a RCT comparing the Promus Element stent with the Promus stent; the study includes prespecified small-vessel and long lesion subgroups and completed enrolment in September 2009. The Perseus trials studying the Taxus Element stent include Perseus WH (Work Horse) and SV (Small Vessel) studies; the former was a 1264-patient RCT comparing the Taxus Element with the Taxus Express, and the latter a smaller 224-patient single-arm trial comparing the small vessel (≤2.75 mm diameter) Taxus Element with historical controls in the Taxus V study. Both trials finished recruiting in October 2008, and although data will not be presented until later in the year, no safety concerns have arisen thus far from independent safety monitoring.

Summary & Conclusions

Novel stent designs and modifications have often promised to deliver tangible clinical improvements, but strut thickness aside, none of these have translated into measurable differences in clinical performance or patient outcomes. The new PtCr alloy has facilitated development of a thin-strut stent design with preserved radial strength that will carry established drug/polymer combinations, and will likely deliver performance that is at least as good as the current Promus/Taxus Liberte designs in forthcoming trial data. Whether this novel alloy/design platform delivers performance improvements over currently-available DES will remain to be seen in clinical trials in due course; only then will we be able to judge whether this alloy deserves the prestige and exclusivity that are connotations of its constituent precious metals.

References

1. Lau K-W, Mak K-H, Hung J-S et al. Clinical impact of stent construction and design in percutaneous coronary intervention. Am Heart J 2004; 147: 764-73.
2. Kastrati A, Mehilli J, Dirschinger J et al. Intracoronary stenting and angiographic results: strut thickness effect on restenosis outcome (ISAR-STEREO) trial. Circulation 2001; 103: 3816-21.
3. Kastrati A, Schomig A, Dirschinger J et al. Increased risk of restenosis after placement of gold-plated stents. Circulation 2000; 101: 2478-83.
4. Koster R, Vieluf D, Kiehn M et al. Nickel and molybdenum contact allergies in patients with coronary instent restenosis. Lancet 2000; 356: 1895-7.
5. Kereiakes DJ, DJ, Cox DA, Hermiller JB et al. Usefulness of a cobalt chromium coronary stent alloy. Am J Cardiol 2003; 92: 463-66.
6. Sketch MH Jr, Ball M, Rutherford B et al. Evaluation of the Medtronic (Driver) cobalt-chromium alloy coronary stent sytem. Am J Cardiol 2005; 95: 8-12.
7. Craig CH, Friend CM, Edward M et al. Mechanical properties and microstructure of platinum enhanced radiopaque stainless steel (PERSS) alloys. J Alloy Comp 2003; 361: 187-99.
   

Dr Adrian Banning, Consultant Cardiologist, John Radcliffe Hospital, Oxford, UK

New coronary stents- Back to the future?

Nobody can dispute the impact that drug eluting stent technology has had upon coronary intervention. Effective modulation of the healing process within the stent has allowed interventionalists to treat long areas of atheroma with multiple stents and achieve results which can be compared with the effectiveness of a surgical bypass graft During this revolution we have all become familiar with the complex performance measures of the polymer(which modulates the release) and the drug combination – in particular the concept of late loss which is a measure of the amount of neointimal tissue one might expect to find within a stent at the end of the healing process. Much emphasis has been placed on these figures and considerable debate has surrounded what a “desirable” late loss might be and in particular how this might relate to rates of very late stent thrombosis.

During 2010 both of the first generation drug eluting stents are scheduled for replacement. Boston Scientific will replace Taxus Liberte with the Taxus Element and Cordis Johnson and Johnson will replace the Cypher Select with the Nevo. Boston will also launch the Promus Element. The principal rationale for these changes is not to change the drug, but to improve the mechanical performance of the stent. Using thinner struts should reduce the biological signal to the vessel to produce neointima which may be clinically beneficial. But considerable emphasis is now being placed on issues which we have almost forgotten about with our concentration on different drugs and polymers. These include the need for the stent to scaffold the vessel to prevent tissue prolapse between the struts and optimising stent visibility to allow accurate positioning of a second stent and post dilation. However, perhaps the most important is the key issue of improved deliverability. It is hoped that these new stents will track better and fewer will end up being wasted. When a stent cannot be implanted in the patient due to vessel tortuosity and a different more flexible bare metal stent has to be used as an alternative, the cost of the wasted drug eluting stent is borne by the hospital as it is not refunded by the purchasers. Improved flexibility may also mean that interventionalists may be more confident to use one long stent rather than two short ones in difficult cases. These practical issues are rarely discussed in international meetings but they are real world issues when we are calculating the cost per case within our increasingly cash restricted Catheter labs.

With the availability of these new stents imminent, I suspect we will be going back to some of the debates we heard last heard in the late 1990s about stent flexibility and deliverability rather than the rather sterile discussion about the decimal points of late loss and rates of late stent thrombosis.