April 9, 2011 - The Resolute zotarolimus-eluting stent using a new biocompatible polymer achieved a lower rate of restenosis and in-stent thrombosis compared to the Endeavor stent at 12 months in a U.S. trial. Data from the RESOLUTE U.S. trial was presented this week at the American College of Cardiology (ACC) Scientific Session in New Orleans.
Out of 1,112 patients who received the Resolute stent, only two cases of stent thrombosis were reported.
“This is one of the lowest stent thrombosis rates we have ever seen in a drug-eluting stent trial,” said Martin Leon, M.D., associate director of the Center for Interventional Vascular Therapy and professor of medicine at Columbia University/New York Presbyterian Hospital.
The Resolute stent’s rate of target lesion failure (TLF) at 12 months was 3.7 percent, compared with 6.5 percent for the historical control patients who received the Endeavor stent.
I think Resolute would be the preferred choice,” Leon said, based on the one-year data. “But, we don’t have the long-term follow-up as we do with the Endeavor. However, I feel most patients would be getting the Resolute stent."
The trial met its primary endpoint of non-inferiority to the historical control, the U.S. Food and Drug Administration (FDA)-approved Endeavor stent. It is the first U.S. study to observe the effect of drug elution characteristics on clinical outcomes. Both the Endeavor and 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). This extended release is hypothesized to better prevent vessel renarrowing while still maintaining low stent thrombosis rates.
“The Resolute drug-eluting stent was shown in this study to deliver strong efficacy without a trade-off in safety through one year of patient follow-up,” Leon said. “The clinical results achieved with this new device show the important role that biocompatible polymers play in the design of drug-eluting stents.”
Enrolling 1,402 patients across 116 U.S. investigational centers between August 2008 and December 2009, the research team conducted four analyses. The main study included 1,112 patients who received Resolute stents that were 2.5-3.5 mm in diameter. The primary endpoint for this group was 12-month target lesion failure (TLF – which combines the composite of cardiac death, target-vessel heart attack and clinically-driven target lesion revascularization). Clinical follow-up was performed at 30 days, six months, nine months and 12 months; it will continue at 18 months and annually thereafter through five years post-procedure.
The researchers compared the data from this main study group with historical data pulled from clinical trials of the Endeavor stent. In order to make accurate comparisons, the team used similar inclusion characteristics, data collection methodologies, endpoint definitions and statistical analyses. They used propensity score method to adjust for baseline covariates.
After conducting this analysis, the research team found that the Resolute stent’s rate of TLF at 12 months was 3.7 percent, compared with 6.5 percent for the historical control patients who received the Endeavor stent, meeting the study’s pre-set margin of non-inferiority (rate difference equals -2.8 percent, upper one-sided 95 percent confidence interval -1.3 percent, p
After looking at the individual components of the primary endpoint, the team found that the Resolute stent also had lower rates of target lesion revascularization, cardiac death and target-vessel heart attack, at 2 percent, 0.4 percent and 1.3 percent, respectively (compared to 4 percent, 0.8 percent and 2.4 percent for Endeavor).
Evaluation of the entire 1,402-person study group (which included patients with one or two lesions who received stents ranging from 2.25 mm to 4 mm) also showed strong outcomes for the Resolute stent, including a 4.7 percent rate of target-lesion failure and a 0.1 percent of definite or probable stent thrombosis. The overall population included 34 percent diabetic patients, the highest to date in any of the Resolute trials.
“The outcomes achieved in the diabetic group are better than expected and we can postulate that the Resolute’s prolonged drug elution profile may contribute to these favorable outcomes in this high-risk group,” Leon said.
Although the study was not a randomized trial, the researchers noted that the propensity score method did allow the team to adequately estimate the effect of changing one of the stent’s three components.
The study was funded by Medtronic. Leon serves on the scientific advisory board for Medtronic.
This study was published online this week in the Journal of the American College of Cardiology (JACC) and will appear in the April 26, 2011, print edition.