Resolute Integrity: New Zotarolimus-Eluting Stent Gains FDA Approval
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A new zotarolimus-eluting stent, Resolute Integrity, has been approved by the US Food and Drug Administration (FDA) for treatment of coronary artery disease (CAD). Cleared on February 17, 2012, it is the first drug-eluting stent (DES) to carry an indication for use in patients with diabetes.
“Having the diabetic indication in part brings attention to the increasing prevalence of diabetes in our patients, [as well as] the narrowing of the gap in outcomes between diabetic and nondiabetic patients who are treated with very effective DES like Resolute,” said David E. Kandzari, MD, of the Piedmont Heart Institute (Atlanta, GA), in a telephone interview with TCTMD.
Resolute Trials Demonstrate Safety, Efficacy
The approval of Resolute Integrity (Medtronic CardioVascular, Santa Rosa, CA) was based on results from a series of studies involving the Resolute DES in a broad spectrum of patients. Resolute Integrity is similar to Resolute except for the sinusoidal configuration of its platform, which is designed to make it more deliverable.
In the European RESOLUTE All Comers study, patients with symptomatic CAD, including both chronic, stable CAD and ACS with or without ST-segment elevation, were randomized to Resolute (n = 1,150) or the everolimus-eluting Xience V stent (n = 1,150; Abbott Vascular, Abbott Park, IL). Notably, 66% of patients in the trial received a DES for at least 1 off-label indication. Baseline characteristics were similar between groups.
At 1 year, Resolute proved noninferior to Xience for the primary endpoint of target lesion failure (TLF; composite of cardiac death, target-vessel MI, or clinically indicated TLR) within 12 months, and there were no differences between the 2 stents for any individual component. Moreover, the likelihood of experiencing TLF did not differ for a variety of subgroups, including those with diabetes, acute MI within 72 hours, bifurcation lesions, and vessels ≤ 2.75 mm. At 2 years, similar safety and efficacy outcomes were sustained between the 2 groups.
In RESOLUTE US, 1,402 patients were enrolled at 128 US-based clinical trial sites. At 1 year, both groups showed low rates of TLF, clinically driven TLR, and definite/probable stent thrombosis.
In a prespecified analysis, 1-year follow-up of the one third of diabetic patients who received Resolute also demonstrated low rates of TLF (6.6%), TLR (3.4%), and definite/probable stent thrombosis (0.3%).
Dr. Kandzari said another novel feature of the Resolute stent is the timed elution of the zotarolimus, which sets it apart from other DES such as Xience or Promus (Boston Scientific, Natick, MA).
“Unlike Xience or Promus, in which everolimus is eluted over about a 60-day period . . . the Resolute stent elutes zotarolimus over 6 months after stent implantation,” he said. “Recognizing the complexities of healing and likely greater neointimal hyperplasia in diabetic patients, a more prolonged drug elution profile may in part translate to the observed benefit. However, this is entirely hypothetical at this point.”
Contending with a Crowded DES Market
Aside from the distinction of having a diabetes indication, however, Resolute Integrity enters a crowded DES field bearing equivalency to the most widely used device, Xience.
“One thing [the new] stent has in its favor is that it addresses many issues of deliverability and various metrics that are important to interventionalists,” Dr. Kandzari observed. Resolute Integrity uses sinusoidal technology to increase flexibility, range of motion, and ease of navigation.
Dr. Kandzari said while Resolute has the potential to be highly competitive in the current DES market, other potential newcomers, such as bioresorbable devices, may have difficulty showing comparative efficacy.
“That is, we have reached a point where the outcomes now are so low and so favorable and so similar across everolimus-eluting stents and stents like Resolute that it would be very difficult for newer stents to demonstrate superiority,” Dr. Kandzari said.
For example, in RESOLUTE US, stent thrombosis at 1 year occurred in only 2 of 1,402 patients, Dr. Kandzari said. “To show superiority over a rate like that would be virtually impossible,” he said.
TWENTE: More Good News for Resolute
A recently released trial involving Resolute that was sponsored in part by Medtronic but was not part of the FDA’s review is TWENTE. The data, originally presented in November 2011 at the annual Transcatheter Cardiovascular Therapeutics scientific symposium in San Francisco, CA, were published online February 16, 2012, ahead of print in the Journal of the American College of Cardiology.
Researchers led by Clemens von Birgelen, MD, PhD, of Thoraxcentrum Twente (Enschede, The Netherlands), randomized patients with chronic stable CAD or ACS to Resolute (n = 697) or Xience V (n = 694).
At 1 year there were no differences between the 2 groups for the primary endpoint of TVF (cardiac death, target vessel-related MI, or clinically driven TLR; 8.2% for Resolute vs. 8.1% for EES; 95% CI -2.8 to 3.0; P for noninferiority = 0.001) or its components. In addition, rates of definite/probable and definite stent thrombosis were relatively low and similar for Resolute vs. Xience (0.9% vs. 1.2%; P = 0.59 and 0.58% vs. 0%; P = 0.12, respectively).
“The TWENTE results really confirm the consistency of the earlier findings [regarding] Xience and Resolute,” Dr. Kandzari said. “The event rates are nearly identical in this well-designed and well-conducted trial, and they are almost exactly the same as in the Resolute All Comers trial. Again, we are observing here in TWENTE, in a fairly unselected complex population, some of the lowest and most favorable adverse event rates with PCI in general.”
Sources:
1. Medtronic Resolute Integrity Drug-Eluting Stent Obtains FDA Approval for Treating Coronary Artery Disease [press release]. http://wwwp.medtronic.com/Newsroom/NewsReleaseDetails.do?itemId=1329500135294. Accessed February 17, 2012.
2. Von Birgelen C, Basalus MWZ, Tandjung K, et al. A randomized controlled trial in second-generation zotarolimus-eluting Resolute stents versus everolimus-eluting Xience V stents in real-world patients: The TWENTE trial. J Am Coll Cardiol. 2012;Epub ahead of print.
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L.A. McKeown is a Senior Medical Journalist for TCTMD, the Section Editor of CV Team Forum, and Senior Medical…
Read Full BioDisclosures
- TWENTE was funded by unrestricted grants from Abbott Vascular and Medtronic.
- Dr. von Birgelen reports serving as a consultant to and receiving lecture fees or travel expenses from Abbott Vascular, Boston Scientific, and Medtronic.
- Dr. Kandzari reports receiving research and grant support from Abbott Vascular, Boston Scientific, and Medtronic and serving as a consultant for Boston Scientific and Medtronic.
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