Europeans Test Absorbable Metal Stent

By Elizabeth Mechatie

A bioabsorbable metal stent with the potential to cause less intimal hyperplasia and, ultimately, less restenosis than permanent stents is being evaluated in a multicenter European study of patients with chronic limb ischemia who are undergoing angioplasty of infrapopliteal lesions.

The limitations of permanent stents have led to efforts to develop stents that are absorbed by the body after the role of preventing remodeling is complete, with the aim of eliminating the trigger for intimal hyperplasia, said Dr. Marc Bosiers, one of the study's principal investigators. The two main categories of bioabsorbable stents that have been developed are polymer and absorbable metal stents. Polymer stents are easily absorbed, but are limited by an inadequate degree of radial force needed to prevent vessel recoil, he said in an interview.

The absorbable metal stent (AMS), made of an alloy that is mostly magnesium, is designed to overcome the main disadvantage of permanent stents: chronic inflammation, followed by intimal hyperplasia and restenosis, that often occurs over time when metal stents are left in place.

The rationale for using the AMS is that it provides the scaffolding to prevent recoil after dilatation, then begins to dissolve after the 7-14 days needed for active remodeling of the vessel wall to take place, after which it is no longer needed for that purpose, noted Dr. Bosiers of AZ St. Blasius Hospital, Dendermonde, Belgium.

The European trial, the AMS-Insight 1 Study (Bioabsorbable Metal Stent Investigation in Chronic Limb Ischemia Treatment), is a prospective, randomized investigation comparing percutaneous transluminal angioplasty (PTA) alone to PTA plus implantation of the AMS in 117 patients with infrapopliteal lesions and chronic limb ischemia. The primary efficacy end point is the treated vessel's patency at 6 months.

Dr. Bosiers said he has no financial ties to Biotronik, the Berlin-based manufacturer of the stent.

Enrollment was expected to be completed in September. Enrollment in a U.S. feasibility trial of similar patients is expected to begin later this year or in the first quarter of 2007. In a preliminary evaluation of the stent in humans, the AMS was found to be safe and effective for infrapopliteal stenting. The device remained patent and provided enough radial force to prevent vessels from recoiling after insertion, according to Dr. Bosiers.

In this first evaluation of the AMS in humans, 20 patients with symptomatic critical limb ischemia caused by high-grade infrapopliteal stenosis received one or two AMS devices between December 2003 and January 2004.

The absorption process began between day 7 and 10, "which is exactly what we need so that absorption starts after the vessel has finished its positive remodeling," Dr. Bosiers said. If the stent starts to be absorbed too early, it does not provide enough support for the vessel.

He and his associates found that the AMS was completely absorbed in about 6-7 weeks. At 3 months, patency was 89.5% and no major or minor amputations were necessary, for a limb salvage rate of 100% in the 19 surviving patients (one patient died of a non-procedure-related cause) (J. Endovasc. Ther. 2005;12:1-5). At 24 months, the primary patency rate was 73%, and the limb salvage rate was nearly 95%, he said.

"It's an exciting technology," Dr. Bosiers noted. "And now we have to wait for the [larger study's] results."

"At this point in time, the concept of a stent that scaffolds for 2-3 weeks or so and slowly goes away is very promising," Dr. Kim Hodgson, professor and chair of vascular surgery at Southern Illinois University, Springfield, said in an interview.

Dr. Hodgson is one of the two principal investigators of the U.S. study of the AMS, which he said will evaluate restenosis and limb salvage rates over 9-12 months in patients with severe tibial disease who have limb-threatening ischemia, at about 15 sites. The stent will provide a good opportunity for limb salvage in these patients without surgery, he said.

The stent's maximum diameter is now 3.5 mm, Dr. Hodgson said. He eventually would like to see the stent expanded to larger sizes so that it could be used in larger vessels, such as the iliac, femoral, and renal vessels.

In the future, AMSs could be improved by coating them with drugs, Dr. Bosiers said. "If you combine an absorbable metal stent with an active coated drug, you take care of both the acute intimal hyperplasia, which is caused by vessel wall injury, and chronic inflammation and chronic intimal hyperplasia," when the stent is absorbed.

When asked to comment on this article, Dr. Ron Fairman stated: "There has been an explosion of new endovascular therapies for chronic infrainguinal occlusive disease; however, experienced interventionalists realize different strategies and platforms will be necessary to successfully treat the infrapopliteal segment. There has been widespread dissatisfaction with the outcomes using traditional angioplasty and stenting techniques.

"Infrapopliteal occlusive disease presents distinct challenges compared to the superficial femoral-popliteal artery segment, as well as the coronary bed. This European prospective, randomized study, known as the AMS-Insight 1 Study, will evaluate the efficacy of bioabsorbable metallic stents; promising results will no doubt lead in the short term to the development of larger diameter absorbable stents for both arterial and venous occlusive disease," said Dr. Fairman, chief of the division of vascular surgery, Hospital of the University of Pennsylvania, Philadelphia.