Medical Device Daily

PARIS – Looking back, those writing the history of interventional cardiovascular technology will see the first five years of this century as a period dominated by the emergence of drug-eluting stent (DES) technology. And, it seems clear, they are likely to see 2006-2010 as a period of transition – to new DES systems, or as a path to other evolutionary forms beyond DES still to be described.

A Wednesday morning EuroPCR symposium, titled “Is there a need for another drug-eluting stent,” clearly pointed to this large gray area, with the near-term answer that there is indeed such a need and that there are already indications that the current generations of DES may be rapidly superseded.

The session provided a rather “infomercial”-style format for this approach, however, especially since the devices discussed are made by, or their technology licensed from, BioSensors International (Singapore), which sponsored the symposium.

In this format, you grant the success of an initial or competing technology but then point to areas of questions and problems that continue to emerge with increasing real-world use of these devices and more experience with their flaws. This then lays the foundation for the “new-and-improved” possibilities.

Listing the flaws of DES is not difficult since these devices, though small in size, offer considerable complexity, especially when placed in the venue of the human body.

That complexity consists of its three-fold structure: the stent itself, a polymer coating used to hold the drug, and the drug. Each of these comes with a range of variables that provide opportunities for negative effects. The stent can come in a variety of scaffolding configurations, thicknesses and lengths, so that correct entry and placement is crucial, though the materials are usually highly inert.

Most of the unintended consequences, according to the presenters, appear to come with the drug or the polymer or the polymer/drug combinations. These may include early- and late-stage thrombus, the side effects that accompany just about any drug, a patient's potential hypersensitivities to drug or polymer, and inflammation.

One potential solution to this is to eliminate the polymer, a strategy employed used in the EAGLE trial described by Thomas Ischinger, MD, professor of Cardiology at Klinikum Bogenhausen (Munich, Germany).

The trial used Biosensors' Axxion technology, employing the company's Calix stent, loaded with paclitaxel by means of a glycocalix substrate but no polymer.

Ischinger noted fast drug elution – 40% to 50% in the first week in a proof-of-principle study – and termed it “a very safe stent in our hands.” He said that safety was the primary benefit since the paclitaxel drug apparently offered no additional benefit over other paclitaxel-eluting products.

Peter Fitzgerald, MD, of Stanford University (Palo Alto, California), provided a look at an analogous strategy, a polymer that rapidly biodegrades, as used in the STEALTH (Stent Eluting A9 BioLimus Trial in Humans) trial, thus leaving a bare metal stent but neither polymer nor drug.

He highlighted the use of another device approach being developed by Biosensors . That device, he noted, utilizes an asymmetrical coating of drug, with 40% to 50% of “the drug load” gone after 180 days and both drug and polymer gone, leaving the bare metal stent, in six to 12 months.

Pointing to effects aside from that of restenosis, Fitzgerald noted the high level of efficacy of bare-metal stenting as compared to DES.

Martin Leone, MD, of the New York Presbyterian Hospital /Columbia University Medical Center (New York) and well-known as one of the most vocal physicians promoting the “disruptive” and game-changing capabilities of DES technology, noted the history-making uptake of DES technology in the device arena.

Leon provided an overview of the stent system from Xtent (Menlo Park, California) which serves to address the fact that a single DES doesn't fit all anatomies and that there is frequent need for more than one stent and more than one procedure.

(Befitting the “infomercial” approach, Xstent licenses a bioabsorbable polymer from Biosensors and its drug formulation from Biosensors' subsidiary Occam International [Eindhoven, the Netherlands]).

The Xtent system is bannered as offering a “customizable” approach to stenting and the ability to place different stent lengths (as opposed to multiple stents) in one procedure or multiple stents with one device and without multiple procedures. Though the technique used to deliver and conform the stent to the customizable shapes and lengths appears complex, he noted easy deliverability.

Still another indicator of future research paths in assessing DES technology was David Holmes, MD, of the Mayo Clinic (Rochester, Minnesota), laying out the problems with the accepted mode of scientifically rigorous clinical trials. Interestingly, he pointed to the difference between “hard” and “soft” trial endpoints and observing that the soft endpoints of patient satisfaction may actually be more important than the hard endpoints of angiographic analysis.

His conclusion – serving as base-line advice to the meeting's interventionalist attendees: “A 'P' value does not substitute for a brain.”

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