NEW ORLEANS--The Resolute (Medtronic) drug-eluting stent (DES) achieved a low rate of clinical restenosis, while maintaining low rates of important safety events at 12 months in a U.S. patient population, according to the RESOLUTE U.S. late-breaking clinical trial presented April 4 at the American College of Cardiology’s (ACC) 60th annual scientific sessions.
According to the researchers, the RESOLUTE U.S. trial is the first U.S. study to observe the effect of drug elution characteristics on clinical outcomes. Both the Endeavor and the Resolute stents are designed with the same cobalt chromium platform and use the same drug (zotarolimus), but the Resolute uses a new biocompatible polymer that allows for an extended drug release across approximately six months (compared to a 14-day release with Endeavor).
Martin B. Leon, MD, director of the Center for Interventional Vascular Therapy at New York-Presbyterian Hospital/Columbia University Medical Center in New York City, and colleagues recruited patients with de novo native coronary lesions suitable for two- or three-vessel treatment with stents from 2.25 to 4 mm in diameter at 116 U.S. investigational centers. In the main analysis cohort (2.5- to 3.5-mm stents and single-lesion treatment), the primary endpoint was 12-month target lesion failure (TLF) defined as the composite of cardiac death, MI and clinically driven target lesion revascularization (TLR), compared with data from Endeavor zotarolimus-eluting stent trials, adjusting for baseline covariates through propensity scores.
From Aug. 21, 2008, to Dec. 16, 2009, the researchers enrolled 1,402 patients with a mean reference vessel diameter of 2.59 mm and diabetes prevalence of 34.4 percent. In the main analysis cohort, TLF was 3.7 percent at 12 months compared with historical Endeavor results (TLF = 6.5 percent). The Resolute stent met the 3.3 percent margin of non-inferiority (rate difference = -2.8 percent). The overall TLF rate was 4.7 percent, and rates of cardiac death, MI and TLR were 0.7 percent, 1.4 percent and 2.8 percent, respectively.
The 12-month rate of definite or probable stent thrombosis was 0.1 percent. “This stent thrombosis rate in 1,400 patients is strikingly good, and therefore, this study may put to bed any lingering safety questions,” Leon told Cardiovascular Business News.
While the study is not powered to truly assess diabetes, the trial had a “higher proportion of diabetic patients than prior studies” at 34 percent, wrote the study authors in the Journal of the American College of Cardiology, where the study was simultaneously published. Three hundred seventy-four patients with 2.5 mm to 3.5 mm stents and diabetes mellitus from the clinical cohort were included in a pre-specified diabetic analysis.
“The percentage of diabetics in RESOLUTE U.S. at 34 percent is a little bit high, but not that different than general U.S. population, which varies from the high 20s to the low 30s, with about a third to a quarter being insulin receiving diabetics,” Leon said. “This may have had a slightly higher diabetic population because they studied patients with smaller vessels, requiring the 2.25 mm stent. And, in these patients, there were surprisingly good results, with a one-year TLF rate of 4.3 percent and TLR rate of 3 percent.”
“Based on the pharmacokinetic profile of this stent, which extends the drug release out to six months, it may in fact perform better in diabetics, but since it’s not powered for this, it is only hypothesis-generating at this time,” he said.
The one-year dual-antiplatelet therapy adherence was 93 percent in the RESOLUTE U.S. trial, which is higher than real-life clinical practice, so it may raise questions about how translatable these results will be to real-life clinical practice. Leon speculated that it is closer to 85 percent in clinical practice.
In JACC, the researchers noted that this is the first study “to evaluate the direct impact of drug elution characteristics on clinical outcomes, using identical drug-eluting stents except for a new polymer that extends drug elution.”
Medtronic funded the study.