RESOLUTE US: Next-generation zotarolimus-eluting
stent exhibits low rate of target lesion failure with minimal stent thrombosis
Expanding on European clinical trials, researchers
found that the Resolute® stent 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 research presented at
the ACC.11 and published in the April 26 edition of the Journal
of the American College of Cardiology.
The RESOLUTE U.S. trial met its primary endpoint
of non-inferiority to the historical control, the 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®
stent and the Resolute® stent 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," said Martin B. Leon,
M.D., associate director of the Center for Interventional Vascular
Therapy and Professor of Medicine at Columbia University/New York
Presbyterian Hospital. "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; 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 <0.001).
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 2.0 percent, 0.4 percent,
and 1.3 percent, respectively (compared to 4.0 percent, 0.8 percent,
and 2.4 percent for the historical control Endeavor® patients).
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 4.0 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.
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