A Medical Device Daily
William Wijns, MD, co-principal investigator of the ENDEAVOR II pivotal clinical trial of Medtronic's (Minneapolis) Endeavor drug-eluting coronary stent, presented positive results Sunday during the American College of Cardiology's (ACC; Bethesda, Maryland) annual scientific sessions.
Wijns said the study demonstrated clinically and statistically significant improvement in all of its endpoints, including a 47% reduction in the primary endpoint of target vessel failure (TVF).
The Medtronic-sponsored study was a randomized, double-blind pivotal trial designed to evaluate the safety and efficacy of the Endeavor stent compared to Medtronic's Driver Cobalt Alloy Coronary Stent in patients with coronary artery disease.
"Overall the clinical results are impressive and show that more than 95% of the patients who received an Endeavor stent in the trial required no further treatment or revascularization at the original treatment site at the nine-month assessment period," said Wijns, co-director of the Cardiovascular Center at OLV Ziekenhuis (Aalst, Belgium). "The Endeavor stent's performance in this trial provides substantial evidence that [it] is safe and that it substantially reduces clinical restenosis compared to a bare-metal stent."
Wijns said these clinical results, "taken together with the ease of use of the Driver stent platform, establish the Endeavor stent as a valuable treatment option for patients undergoing angioplasty with drug-eluting stents."
The trial enrolled 1,197 patients at 72 facilities in 17 countries, making it the first and largest drug-eluting stent trial comparing a drug-eluting stent to a bare-metal stent ever performed outside the U.S., according to Medtronic.
The primary endpoint of the trial was TVF at nine months. TVF is a composite endpoint, which includes death, myocardial infarction and target vessel revascularization (TVR). In addition to the 47% reduction in TVF in the Endeavor arm (8.1%) in comparison with the control group (15.4%), the study also demonstrated a 62% reduction in target lesion revascularization (TLR) between the Endeavor arm (4.6%) and the control group (12.1%). TLR is the rate of retreatment of patients after coronary stenting and is viewed by physicians as a critical clinical marker of DES effectiveness.
Medtronic said the results from the trial would be used to support Endeavor product approvals globally.
Angiographic results of the study demonstrated a significant reduction in restenosis rates, with a 71% reduction in in-stent angiographic binary restenosis (ABR) in the Endeavor arm (9.5%) vs. the control arm (32.7%). The in-segment ABR rate in the study was reduced by 61% in the Endeavor arm (13.3%) vs. the control arm (34.2%).
The study also indicated a 50% reduction in the major adverse cardiac event rate in the Endeavor arm (7.4%) compared to the control arm (14.7%). It also showed a 0.5% rate of stent thrombosis at 30 days – with no late thrombosis beyond 30 days and no late stent malapposition.
"These are extremely solid clinical and angiographic results," said co-principal investigator Richard Kuntz, MD, associate professor at Harvard Medical School and chief of the division of clinical biometrics at Brigham and Women's Hospital (Boston).
The Endeavor drug-eluting stent is based on the Driver coronary stent, which is made of a cobalt alloy and features what Medtronic terms "a unique modular architecture to provide enhanced deliverability over standard bare-metal stents."
"With this compelling and definitive data, we look forward to moving on with our efforts to commercialize the Endeavor stent outside the U.S. this spring," said Scott Ward, president of Medtronic Vascular (Santa Rosa, California). "We are ramping up our manufacturing operations to supply the world with readily available product and our distribution network is prepared and ready to bring this product to physicians and patients around the world when approved for use."
He added that the company would present the final results from the ENDEAVOR III trial in October and intends to begin the ENDEAVOR IV trial in the next few weeks.
At a Saturday symposium preceding the start of the ACC meeting, Conor Medsystems (Menlo Park, California) presented angiographic and clinical data from the company's pivotal EuroSTAR study evaluating its CoStar cobalt chromium paclitaxel-eluting stent in what it termed a "complex patient cohort."
The six-month follow-up data, which Conor said demonstrated "positive angiographic and clinical results for the treatment of single or multiple de novo lesions in native coronary arteries," were presented by one of the study's principal investigators, Keith Dawkins, MD, director of cardiac interventions at Southampton University Hospital (Southampton, UK), at the DES Revolution IV, a symposium sponsored by the Cardiovascular Research Foundation (New York).
A total of 176 lesions were treated in 145 patients using the CoStar stent formulated to release a therapeutic dose of 10 mcg of paclitaxel over about 30 days (based on in vitro measurements). Characteristics of the patient group include diabetes in 16% of patients, an average vessel diameter of 2.64 mm, and multi-vessel disease in more than 50% of patients. About 52% of the lesions were treated by direct stenting.
At six-month follow-up, the in-stent binary restenosis rate was 3.4% and the in-stent late loss was 0.26 mm. The in-segment binary restenosis rate was 4.7% and the in-segment late loss was 0.07 mm. As Conor has reported previously, the target lesion revascularization (TLR) rate was 1.7% and the rate of cumulative MACE was 4.8.
"The results of this trial demonstrate consistently low restenosis and complication rates for the CoStar stent across an array of patients," said Dawkins.
In contrast to conventional surface-coated stents, Conor has emphasized that the CoStar stent has been specifically designed for vascular drug delivery. Its de-sign incorporates hundreds of small holes, each acting as a reservoir into which drug-polymer compositions can be loaded.
Conor said its stent design enables a wider range of drug therapies, including combinations of multiple compounds, and provides greater control over the direction and rate of drug release, which it believes allows for more targeted treatment within the artery and more efficient use of the therapeutic agent.
"We're very pleased to report the encouraging follow-up angiographic results as we continue to demonstrate the safety and clinical benefits of [the] CoStar," said Frank Litvack, MD, chairman and CEO of Conor. "In addition, we have received positive feedback from our investigators on the ease of delivering our cobalt chromium stents in patients with diverse vessel characteristics."
He added: "The novel design of our non-surface coated stents, with their proprietary ductile hinges and drug reservoirs, allows for enhanced control over the rate and duration of drug delivery, which we believe provides for optimal drug release and sustained stent performance."