RESOLUTE US Looks at Latest-Generation Zotarolimus Stent

NEW ORLEANS, LA—A novel zotarolimus-eluting stent offered low restenosis rates and demonstrated clinical safety in its first US experience. The findings from RESOLUTE US were released in a late-breaking clinical trial session April 4, 2011, at the American College of Cardiology Scientific Session/i2 Summit and simultaneously published online ahead of print in the Journal of the American College of Cardiology.

The RESOLUTE All Comers trial, presented a day earlier, demonstrated that the zotarolimus-eluting Resolute stent (Medtronic, Santa Rosa, CA) had similar safety and efficacy compared with the everolimus-eluting Xience V stent (Abbott Vascular, Santa Clara, CA) through 2-year follow-up.

Presenting results from the RESOLUTE US trial on Monday, Martin B. Leon, MD, of Columbia University Medical Center (New York, NY), explained that Resolute is largely similar to Medtronic's Endeavor stent with the exception of its hydrophilic polymer, which extends drug elution as long as 6 months. It produces “biologically available doses of drug in tissue that could induce prolonged antiproliferative effects,” he said.

Documenting Outcomes with Novel Stent

The prospective observational study looked at patients with de novo native coronary lesions suitable for 1- or 2-vessel treatment with stents ranging from 2.25 to 4.0 mm in diameter. Overall, 1,402 patients were enrolled, with a mean reference vessel diameter of 2.59 ± 0.47 mm and diabetes prevalence of 34.4%. Approximately 10% of patients were treated for disease in 2 vessels.

The main analysis focused on 1,001 patients implanted with 2.5- to 3.5-mm stents in single lesions. Their results with Resolute were compared with those of historical controls derived from earlier trials that tested Endeavor, including ENDEAVOR II, ENDEAVOR IV, ENDEAVOR PK, and ENDEAVOR II Continued Access. At 12-month follow-up, the primary endpoint of target lesion failure (TLF; composite of cardiac death, MI, and clinically-driven TLR) was 3.7% for Resolute and 6.5% for historical controls (P < 0.001 for noninferiority).

In the overall cohort, adverse outcomes rates were “somewhat lower” than what has been seen by other trials of Resolute, said Dr. Leon (table 1).

Table 1. Clinical Outcomes for All Patients

 

At 30 Days
(n = 1,398)

At 1 Year
(n = 1,376)

TLF

1.4%

4.7%

Death

0.1%

1.3%

MI

1.2%

1.4%

Clinically-Driven TLR

0.1%

2.8%

Clinically-Driven TVR

0.4%

4.6%

Stent Thrombosisa
Early (≤ 30 Days)
Late  (> 30 to ≤ 360 Days)

 
0.1%
N/A

 
0.1%
0.1%

a Academic Research Consortium-defined definite or probable stent thrombosis.

At 8 months, angiographic outcomes also were favorable. The in-stent and in-segment binary restenosis rates were 9.2% and 9.8%, while in-stent and in-segment late loss were 0.30 ± 0.54 mm and 0.20 ± 0.43 mm, respectively. An IVUS substudy found a 1.7% incidence of late acquired incomplete apposition and percent volume obstruction of 5.34 ± 5.97.

“The Resolute zotarolimus-eluting stent has been studied now in over 5,000 patients under varying conditions in a global clinical trial program,” Dr. Leon commented. “The RESOLUTE US data add to this accumulating experience by providing rigorous clinical and angiographic outcomes in a diverse US population, enriched with small and large vessels, multivessel disease, and frequent diabetes.” However, longer follow-up is necessary, he added.

Overall, the findings indicate that Resolute “has achieved benchmark performance standards for safety and effectiveness among currently available drug-eluting stents,” Dr. Leon concluded.

Only Good News for Resolute

Panel member Alexandre Abizaid, MD, PhD, of the Instituto Dante Pazzanese (São Paolo, Brazil), said he was pleasantly surprised by the low rate of stent thrombosis observed in RESOLUTE US compared with the 1.7% rate seen within the same follow-up duration in RESOLUTE All Comers.

“We struggle with these interstudy comparisons when you have a low event rate phenomenon like stent thrombosis,” Dr. Leon replied. “Each case is its own story. There's a lot of variation with adjudication. We were surprised and there was anxiety associated with the RESOLUTE All Comers study suggesting that there may have been a higher early stent thrombosis rate than we expected, certainly compared to Xience in that patient population.”

The solution, he said, is to accumulate a substantial body of carefully adjudicated data in order to fully understand stent thrombosis. Although the numbers will vary by chance, Dr. Leon said, the 0.1% finding is encouraging.

“I'm sure that after these data you're going to have Resolute approved in the US, if I may speculate on that,” Dr. Abizaid predicted. “If you do, and you also have Endeavor on your shelves, what kind of clinical indication would you use to choose one stent vs. another?”

Dr. Leon replied, “Clearly, the comparisons in this study indicate that from the standpoint of antirestenotic efficacy, either clinical or angiographic, Resolute is a superior stent to Endeavor. So if you have a patient where you're concerned about restenosis, certainly Resolute will be the preferred choice. On the other hand, we don't have enough long-term follow-up data, so if you're concerned more about long-term safety, the ability to persist with dual antiplatelet therapy in the patient, you might favor the Endeavor stent. . . I imagine the majority will get the Resolute stent.”

Session co-chair George D. Dangas, MD, PhD, of Mount Sinai Medical Center (New York, NY), asked Dr. Leon where Resolute fit in comparison with non-zotarolimus stents.

“I'll be provocative. I think that Xience/Promus and Resolute represent the state of the art in terms of current generation available drug-eluting stents. To choose between them would be very difficult for me. I think they seem to be fairly equivalent in most of the important safety and effectiveness metrics, but they're both superb,” Dr. Leon concluded.

 


Sources:
1. Yeung AC, Leon MB, Jain A, et al. Clinical evaluation of the Resolute zotarolimus-eluting coronary stent system in the treatment of de novo lesions in native coronary arteries: The RESOLUTE US clinical trial. J Am Coll Cardiol. 2011;Epub ahead of print.

2. Silber S, Windecker S, Vranckx P, et al. Unrestricted randomised use of two new generation drug-eluting coronary stents: 2-year patient related versus stent-related outcomes from the RESOLUTE All-Comers trial. Lancet. 2011;Epub ahead of print.

 

 

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Disclosures
  • The RESOLUTE US and RESOLUTE All Comers trials were funded by Medtronic.
  • Dr. Leon reports serving on a scientific advisory board for Medtronic.

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