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Cracking, peeling, and other damage to polymer surfaces can be seen following delivery balloon expansion in all 4 drug-eluting stents (DES) currently on the market, according to a research letter published in the May 23/30, 2012, issue of the Journal of the American Medical Association. The researchers suggest that detachment of micropolymers as a result of surface damage could contribute to DES-associated complications, including thrombosis, restenosis, and microvascular and endothelial dysfunction.

Researchers led by Scott J. Denardo, MD, of Duke University Medical Center (Durham, NC), used optical microscopy to image the polymer surface of the 4 US Food and Drug Administration (FDA)-approved DES:

• Xience V (Abbott Vascular, Abbott, IL)
• Taxus Liberté (Boston Scientific, Natick, MA)
• Cypher (Cordis, Miami Lakes, FL)
• Endeavor (Medtronic, Minneapolis, MN)

A BMS expanded using the same technique served as the control.

The DES manufacturers were identified only as A, B, C, and D.  Five of each stent type were tested in a vacuum filtration system containing a filtered test medium. Stents expanded unconstrained, but under conditions designed to mimic regulatory submission requirements and the variability seen in clinical practice.

The abluminal surface of each stent was imaged prior to expansion, and both the abluminal and adluminal surfaces were imaged after expansion. Damage definitions included:

• Delamination: complete separation of polymer from stent surface
• Ridging: dislocation without detachment but with accumulation of polymer to form an elevated mass on the stent surface
• Webbing: distortion of the polymer such that material is stretched across and partially obstructs an open cell in between stent struts
• Peeling: partial but incomplete delamination of the polymer, which protrudes into the vessel lumen
• Cracking: fine transection through entire polymer thickness

Wide Range of Damage Seen

Prior to balloon expansion, 1 DES type showed cracks on the abluminal polymer surface. Following balloon expansion, the abluminal and adluminal surfaces of all 4 DES were damaged, affecting 4.6% to 100% of the surface area imaged. All 4 DES had ridging, while 3 had peeling and cracking, 2 had delamination, and 1 had webbing. Microparticles were shed by 3 DES. BMS had no such damage.

The dimensions of damage and detached microparticles ranged from 2 to 350 µm, and microparticles from all except DES B were confirmed to be polymer. The extent of damage differed by manufacturer (P < 0.001 for adluminal damage, P < 0.002 for abluminal damage).

No Basis for Comparison

In a telephone interview with TCTMD, Dr. Denardo said that while stent thrombosis and restenosis have already been thoroughly researched, complications including microvascular and endothelial dysfunction “have not been fully explained.”

Although the stent manufacturers were deidentified in reporting of the results, he said, the stents with the most damage have been associated with higher rates of both thrombosis and restenosis. Additionally, microvalvular and endothelial dysfunction coordinated with the amount of microparticles generated.

Since the FDA has only recommended and not required this type of research be conducted, there is a lack of information to draw strong conclusions at this time, Dr. Denardo cautioned.

“It would be a good idea to take the next step and document if the microparticles cause a problem or not, and I would zero in on the microvascular dysfunction,” he said. “It’s kind of been left in the hands of the vendors to do this research; and whether or not they’re doing this, they are not publishing the results. It would be useful if we had a better understanding of [whether] there are problems and if the vendors are doing anything about it.”

Nothing New, Relevant

However, Sorin J. Brener, MD, of Weill Cornell Medical College (New York, NY), told TCTMD in an interview the relevance of this research is questionable, especially since all of the stents studied are first- or second-generation devices rather than newer models.

When DES were first used, “everyone talked about this . . . and said it’s unlikely that this polymer would be perfect,” he said.

Dr. Brener expressed surprise that 1 of the stents was cracked preimplantation but questioned if that observation even had meaning.

“It depends on your outlook on life,” he said. “The way I look at it, we have the Xience stent with so few events, no stent thrombosis, so I would say it probably doesn’t matter, but I don’t know for sure.

Although the manufacturers were deidentified, he said that the stents could easily be identified by looking at the stent strut shapes provided in the images accompanying the research letter. In fact, he suggested that DES B was Taxus, which would make sense he said, because of the webbing that occurred in that stent.

“That could explain this issue of side branch occlusion, which was more common with the Taxus stent for years,” he said. “But this is what we always said. The reason there has been more periprocedural MI and more side branch occlusion with Taxus is because of this redundant polymer.”

Source:

Denardo SJ, Carpinone PL, Vock DM, et al. Changes to polymer surface of drug-eluting stents during balloon expansion. JAMA. 2012;307:2148-2150.

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