Can Better Polymers Challenge DES? Cost Barriers Spur German Alternative

Coronary stents coated with non-carbon-based polymers may prevent restenosis without bearing drugs, Götz Richter, MD/PhD, University of Heidelberg, Germany, asserted Nov. 18.

During the annual VEITH Symposium in New York Nov. 18, the radiology professor presented work on a "polyphosphaze" polymer. Richter's talk was titled "Can Restenosis Be Prevented Without Drugs: Drug-Eluting Stents Are Not Needed."

"The polymer is really of concern, and this is how we came across an entirely new substance...which allows us to use nanotechnology," he explained. It "is not a carbon-based polymer; it has a central phosphorus atom, and that all comes together with a negative surface charge, which makes it chemically resistant."

Further, "because of the nanotechnology, it can be applied as thin as 50 nanometers," Richter said. The high-purity, hydrophobic polymer allows low platelet adhesion, he noted.

Addressing an audience of vascular interventionalists, he alluded to a "huge body of evidence that shows that we shouldn't be convinced that drug-eluting stents are really the future." According to Richter, early porcine study data show the novel coating to yield zero stenosis, compared with eight out of 10 stents in the control group - a result he observes is statistically significant.

"We think this coating shows some promise because it can prevent early thrombosis and it provides very little in-stent stenosis, which is in the range of active drug-eluting stents. And this material has future potential if you look at enhanced biocompatibility. We're doing adhesion tests to see if healing occurs," he said.

Richter's desire to study stent polymers grew from health economics. DES "market penetration may be 80% in the U.S., but in Germany it's only 15%. That's because drug-eluting stents are so expensive, and that's why we're looking for ways to improve other things which may not be as expensive as a drug-eluting stent."

Julio Palmaz, MD/PhD, University of Texas at San Antonio, agreed the future could hold a non-drug-based nanotechnology solution. "We can take a material that is plain and conventional and make it into something that is outperforming or is at least having a dramatic response with nanotechnology," he declared. "The changes in the future will be mechanistic. We will target a molecular mechanism, the same way you do with drugs." Palmas is co-inventor of the original coronary stent, made by J&J.

Palmaz averred that substantive changes to coronary stent design are over, echoing a sentiment he voiced at TCT 2004 (¹ (Also see "Stent Inventors Swap Design Tips: Struts, Surfaces Continue To Evolve" - Medtech Insight, 18 Oct, 2004.), p. 17). "But when you come to polymers, there are hundreds of them, perhaps thousands, because polymers go forever - you can keep modifying them."

"The new avenue will be an alliance between surface technology and molecular biology," Palmaz suggested. "[We] definitely will have to get into territories that are not familiar to the engineer, but rather to the physical chemist. We need to learn to study new possibilities."

At the meeting, Ron Waksman, MD, Washington Hospital Center, and Renu Virmani, MD, Armed Forces Institute of Pathology, resumed their ongoing critique of drug-eluting stents. Waksman maintained "there is still some restenosis with drug-eluting stents [for which] brachytherapy can bail you out."

"Brachytherapy is currently the most effective modality to prevent restenosis in the [superficial femoral artery] and for treatment of in-stent renal stenosis. We have to tailor the dose to the vessel size, specifically for the largest vessels, and we have to keep anti-platelet therapy to make sure that we don't encounter any late thrombosis," he said. "Don't be seduced by drug-eluting stents. If you have restenosis, brachytherapy will always stay by your side."

The brachytherapy market is viewed by many to be on the verge of collapse, given DES market dominance. The most prominent manufacturer in the field, Novoste, is burning through its cash reserves at $1 mil. per month due to losses (² (Also see "Novoste CEO’s Challenge: Stabilize Brachy Biz Or Ink Merger While Cash Lasts" - Medtech Insight, 8 Nov, 2004.), p. 26).

Virmani cautioned against DES adverse events. With Boston Scientific's Taxus , her agency has seen "thrombosis, we've seen fibrin deposition around the struts. And we've seen mild to moderate inflammation as well." With J&J's Cypher , "we've seen three cases of occlusive thrombosis. We've also seen...hypersensitivity reaction in two cases, one with occlusive and one non-occlusive - one short-term, one long-term." Animal studies show hypersensitivity reactions induced in animals - "more so with Taxus than Cypher - probably related to the polymer used," she said. "The ideal stent is one that does not use a polymer and uses a non-toxic statin drug, which we do not have at the moment."