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New Drug-Eluting Stent Okayed for Diabetics
Medtronic's Resolute Integrity Stent is First and Only Drug-Eluting Stent
with FDA Approval for Use in Diabetic Patients
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Medtronic's Resolute Integrity Stent
February 27, 2012 -- What was an "off label" use of drug-eluting stents only a week ago is now "on label" -- the FDA has approved Medtronic's new zotarolimus-eluting stent, the Resolute Integrity, specifically for use in diabetic patients, a population that historically has seen less than optimal outcomes for percutaneous coronary interventional procedures (PCI). The paradox is that diabetes by itself is a major risk factor for developing coronary artery disease -- CAD is the cause of death for almost 60% of diabetic patients -- yet it has been difficult to treat diabetic patients for CAD because they tend to have smaller coronary arteries and elevated blood-sugar levels, which can increase the rate of procedural complications and long-term safety risks.

Managing Coronary Artery Disease (CAD) in Diabetic Patients
Treatment for managing CAD in diabetic patients includes taking prescribed medications, making lifestyle changes, such as exercise, diet, smoking cessation and weight loss. However, if CAD progresses and arteries become significantly blocked, angioplasty/stenting or bypass surgery may be utilized. Until now, surgery has been the preferred treatment for two reasons: (1) in randomized stent trials and registries, the diabetic patients have not fared as well as those without diabetes; and (2) use of any stent, bare metal or drug-eluting, has been "off label" -- not approved for this use by the FDA.

New Stent Safe and Effective for Diabetics
In order to achieve the FDA approval for diabetics, Medtronic started trials over five years ago and to date has looked at over 5,100 patients, a larger number and with more complex disease than has previously been done, one-third of whom were diabetic, which mirrors the U.S. patient mix. These studies, previously reported by Angioplasty.Org, include the RESOLUTE All-Comers trial, RESOLUTE US, and the TWENTE trial. The results of these studies showed that the Resolute was comparable to the Xience V stent, currently the leading drug-eluting stent.

However, to achieve the diabetes approval, the stent had to do better in the diabetic cohort. As explained to Angioplasty.Org by Sean Salmon, president of Medtronic's coronary and renal denervation business, there was no significant difference in the outcomes between diabetic and non-diabetic patients:

"In order to get the indication [for diabetes] we had to beat the standard of performance that was based on prior approved stents including Endeavor, Xience, Taxus and Cypher: a 14.5% event rate which we beat pretty handily with a 7.8% rate. We don't see a gradated performance between diabetic and non-diabetic, like some of the products we've seen. And they're really strong outcomes. For hospital and doctors, they don't have to use a product off-label. They don't have to bill for a product that's off label. So it's a nice differentiation and...we've got the science that backs up the claim that it works for those patients.

New Polymer, New Stent Platform
As explained in Angioplasty.Org's Drug-Eluting Stent Overview, three components work together to make an effective stent: the bare metal stent platform, the polymer coating that controls the rate of drug elution, and finally the drug itself which suppresses the formation of excess tissue inside the stent.

The drug zotarolimus has proven effective in Medtronic's Endeavor stent, but the rate of elution has changed in the Resolute, which uses a unique BioLinx Polymer, designed from the ground up. The side of the polymer that makes contact with the arterial wall is hydrophilic and extremely biocompatible, thus minimizing any inflammatory response. But the side of the polymer facing inward to the blood flow is hydrophobic, repelling water, and delaying the drug release, so it occurs over a longer period of time and increases efficacy.

The main studies, started years ago, were done with the Resolute stent, which used an earlier platform: the widely-used Driver bare metal stent. But while these studies were progressing, an entirely new stent design was being engineered, one very different from previous stents: the Integrity stent is made from a single metal strand, a continuous sinusoidal design, hence the name "Integrity." According to Medtronic's Sean Salmon:

"The platform itself has really been a great surprise to a lot of doctors. It's immensely flexible in three dimensions all at one time, not just relying on a hinge joint to get around a corner. The stent elements don't crash into each other at the bottom and "pine cone" up at the top. And the rounded struts slip through the vessel pretty well. Doctors can really rely on getting the product where they want it to go. They can rely on getting the case done without lots of extra equipment to be used and they can get the lab turned over for the next patient. It saves resources, it saves time, and it ensures that they have the confidence to treat the patient, no matter what their anatomical challenges are.

"And the device is flexible both before you deploy and after you deploy it. So it does a really nice job of conforming to the anatomy, giving good continuous scaffolding coverage without gaps in struts against the wall -- or straightening the vessel out, which can be problematic as well. It's a very popular platform and just recently overtook the number one position worldwide and in the United States for a bare metal stent."

The FDA had previously approved the Integrity bare metal stent, so the Agency was able to clear the proven Resolute zotarolimus-eluting polymer on the Integrity platform. Medtronic's new entry into the drug-eluting stent market comes at a time when the use of stents has leveled off, but as Salmon says:

It's only going to go up from here. We've got the most deliverable platform in the market, great clinical data, great clinical organization, and a sales organization behind it, so I think we'll do very well. It's hard to grow in this market, but I think we're the ones who will buck the trend.

Following is an animation of the Resolute Integrity zotarolimus-eluting stent being implanted in a coronary artery, courtesy of Medtronic:

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Resolute Integrity Stent (:31)
Animation, courtesy Medtronic, Inc.

Reported by Burt Cohen, February 27, 2012