A Medical Device Daily

Medical device makers are taking full advantage this week of Transcatheter Cardiovascular Therapeutics (TCT) 2009 in San Francisco by releasing a flood of new clinical data and showcasing their latest and greatest products. Not surprisingly, much of that data relates to drug-eluting stents (DES).

Among the key players presenting DES data, Medtronic (Minneapolis) reported the latest findings from its ENDEAVOR IV trial, a large study comparing its Endeavor zotarolimus-eluting stent and Boston Scientific's (Natick, Massachusetts) Taxus paclitaxel-eluting stent at three years of patient follow-up. Medtronic says the findings demonstrate statistically and clinically significant differences in measures of safety between Endeavor and Taxus. The new data also show no difference in efficacy between the two devices at three years, the company noted.

"The three-year results from ENDEAVOR IV conclusively demonstrate that choice of stent really does matter for patients with coronary artery disease," said principal investigator Martin Leon, MD, of New York-Presbyterian Hospital/Columbia University Medical Center and the Cardiovascular Research Foundation. "As interventionalists, we now have long-term outcomes data that should be critically evaluated when making treatment choices for our patients."

Leon added that, "For several years we have seen a trend toward outstanding safety with the Endeavor stent throughout the clinical program and in pooled analyses. These latest randomized data are the first to show statistically significant differences on hard clinical endpoints that clearly favor one drug-eluting stent over another at three years. Specifically, they show comparable efficacy between the Endeavor and Taxus stents in long-term follow-up, with significant safety advantages for Endeavor patients with regard to a reduction in large myocardial infarctions that are directly attributable to the significantly higher rate of very late stent thrombosis observed with the Taxus stent."

Concerns about the consequences of the higher observed rate of very late stent clotting in drug eluting versus bare metal stents have loomed since 2006 but have been allayed by large, population-based registry data that have not shown an increase in death or myocardial infarction, Medtronic said. According to the company, ENDEAVOR IV represents the first long-term large, head-to-head drug eluting vs. drug eluting stent comparison to demonstrate a statistically significant increase in very late stent clotting and a corresponding significant increase in cardiac death and myocardial infarction. The data definitively show that at three years of follow-up, patients treated with an Endeavor stent have a statistically and clinically significant 48% lower risk of heart attack or cardiac death than patients treated with a Taxus stent and a 91% reduction in the risk of very late stent thrombosis.

ENDEAVOR IV enrolled 1,548 patients, equally randomized to receive an Endeavor or Taxus DES. The primary endpoint in the study was non-inferiority on the measure of target vessel failure – a composite of cardiac death, myocardial infarction and target vessel revascularization – at nine months.

"Medtronic understands that clinical outcomes are what matter to patients, and we are committed to ongoing evidence-based research to develop products that improve people's lives," said interventional cardiologist Richard Kuntz, MD, senior VP of strategy, clinical and regulatory affairs at Medtronic. "These new data from ENDEAVOR IV clearly and compellingly demonstrate that the Endeavor stent should play a much larger role in the care of patients with coronary artery disease."

Meanwhile at TCT, Boston Scientific is presenting data of its own – three-year results from the SPIRIT III trial, which the company says continue to reaffirm the long-term safety of its drug-eluting stents, including the first-generation Taxus Express and the Xience V (Promus everolimus-eluting stent system). Abbott (Abbott Park, Illinois) makes the Xience V everolimus-eluting stent, which won FDA approval in July 2008, but Boston Scientific shares profits from the device. Guidant (Indianapolis) had been developing the stent and when Boston Scientific acquired the company, it had to divest the stent to Abbott, but it retained the right to sell the same device as the Promus under a private-label arrangement (MDD, July 7, 2008).

The SPIRIT III results were presented at TCT by Gregg Stone, MD, professor of medicine and the Director of Research and Education at the Center for Interventional Vascular Therapy at the Columbia University Medical Center/New York-Presbyterian Hospital, and principal investigator of the trial.

"We are very pleased that our first-generation Taxus Express stent continued to perform well against our Promus stent in the SPIRIT III trial at three years," said Donald Baim, MD, chief medical and scientific officer of Boston Scientific. "The strong outcomes among diabetic patients were particularly impressive."

The results demonstrated that the Xience V (Promus) and Taxus Express stents had comparable safety outcomes through three years, with equivalent rates of cardiac death (1.4% versus 1.6%, p=0.68) and low and equivalent rates of stent thrombosis using the Academic Research Consortium definite/probable definition (1.2% and 1.6%, p=0.67). No additional stent thromboses were reported between years two and three for either stent group, the company noted.

The three-year rate of ischemia-driven target lesion revascularization (TLR) was lower for the Xience V stent as compared to the Taxus Express (5.4% versus 8.9%, p=0.05), contributing to a benefit for Xience V over the TAXUS Express in the composite endpoints of Major Adverse Cardiac Events (MACE) and TLR (9.1% versus 15.7%, p=0.003) and target vessel failure (TVF) (13.5% versus 19.2%, p=0.03).

Boston Scientific said the SPIRIT III results exhibited similar rates of safety and efficacy for the Xience V and Taxus Express stents in diabetic patients, with TLR rates of 5.2% versus 4.8% and MACE rates of 10.3% versus 9.4%. The rate of TLR for Taxus Express diabetic patients was 4.8% as compared to 10.5% in non-diabetic TAXUS Express patients.

Interestingly, Boston Scientific also reported comprehensive data from the TAXUS ATLAS clinical program, a series of global, prospective, single-arm trials evaluating the Taxus Liberte paclitaxel-eluting stent system in a variety of lesions and patient groups. Three-year results from the TAXUS ATLAS Small Vessel and Long Lesion Trials continue to show significant advantages for the newer Taxus Liberte stent when compared to the first-generation Taxus Express stent, the company noted.

The TAXUS ATLAS Small Vessel Trial was designed to evaluate the long-term safety and efficacy of the 2.25 mm diameter Taxus Liberte Atom stent in small coronary vessels. The TAXUS ATLAS Long Lesion Trial was designed to assess the long-term safety and efficacy of the Taxus Liberte Long 38 mm stent in patients with long coronary lesions. Boston Scientific said it remains the only company to offer both 2.25 mm diameter and 38 mm length drug-eluting coronary stents in the U.S.

Three-year results from the TAXUS ATLAS Small Vessel Trial demonstrated a statistically significant reduction in the rate of TLR in small vessels treated with the Taxus Liberte Atom stent as compared to the Taxus Express Atom stent (10.0% vs. 22.1%, p=0.008), representing a 55% relative risk reduction. Additionally, the three-year MACE rate for the Taxus Liberte Atom stent was 19.5% as compared to 32.4% for the Taxus Express Atom stent (p=0.03), a relative reduction of 40%. The composite safety measure of cardiac death or heart attack remained numerically lower at three years for the Taxus Liberte Atom stent as compared to the Taxus Express Atom stent (6.5% vs. 7.4%, p=0.79).

In the TAXUS ATLAS Long Lesion Trial, the Taxus Liberte Long stent demonstrated significantly improved safety outcomes when treating long lesions compared to the Taxus Express stent, the company noted. The rate of cardiac death showed a significant 78% reduction in patients treated with the Taxus Liberte Long compared to the Taxus Express (1.5% vs. 6.7%, p=0.03). Overall MI showed a significant 72% reduction at three years in patients receiving a single Taxus Liberte Long stent compared to a single Taxus Express stent (2.9% vs. 10.4%, p=0.01).