SPIRITs Buoyed With New XIENCE V Data: Bests Taxus in Head-to-Head Study

March 26, 2007

March 27, 2007 (New Orleans, LA) – Data on a promising new drug-eluting stent were presented here today at the American College of Cardiology 2007 Scientific Sessions, showing that the XIENCE V stent (Abbott Vascular), a second-generation everolimus-eluting stent, was significantly better than the Taxus (Boston Scientific) paclitaxel-eluting stent in preventing in-segment late loss. In addition, the XIENCE stent was shown to be noninferior to the Taxus stent in terms of preventing a number of clinically important end points.

"The conclusions of the trial are, in terms of angiography, that we were able to show noninferiority and superiority in terms of suppressing late loss, with strong trends toward reductions in binary restenosis," said lead investigator Dr Gregg Stone (Columbia University, New York) during a press conference announcing the results. "In terms of clinical events, we have a stent, the XIENCE V, that is at least as safe and effective according to several of these important efficacy end points--in particular, ischemic target lesion revascularization [TLR] and major adverse cardiac events [MACE], in which it was shown to be superior. So the regulatory hurdles of both the primary and secondary end points were met."

While it is unusual for investigators to comment on the regulatory process, Stone said that clinicians are in need of newer, safer, and more effective drug-eluting stents and that the present study, known as SPIRIT III, was designed with the intention of meeting the earlier approval requirements of the Food and Drug Administration (FDA).

Following in the footsteps of SPIRIT I and II

Speaking with the press, Stone noted that XIENCE V uses an enhanced floral polymer, which is unique in that it is very thin, nonadhesive, and nonsticky, so that it tends not to be associated with adverse polymer effects. The stent used is a low-profile, cobalt-chromium stent with thin struts, making it highly deliverable. The question, said Stone, was whether the polymer and stent would work together.

The SPIRIT III investigators enrolled 1002 patients at 65 US sites. Patients with one or two lesions, 2.5 mm to 3.75 mm in diameter, were randomized in a 2:1 manner to the XIENCE V stent or the Taxus stent. After implantation, patients were treated with clopidogrel 75 mg once daily for at least six months. The primary end point of the study was in-segment late loss at eight months, and the secondary end point was ischemia-driven target vessel failure (TVF), a composite of cardiac death, MI, TLR, and target vessel revascularization (TVR).

"What we found was that late loss, in the analysis segment, the primary end point of the study, was significantly reduced with the XIENCE stent compared with the Taxus stent, from 0.28 mm with Taxus to 0.14 mm with the XIENCE, so essentially cut in half. That not only met the criteria for noninferiority but was also superior," said Stone. "While we were not powered for binary restenosis, there was a strong trend toward a 50% reduction in binary restenosis, a finding that was supported by the IVUS substudy, which showed a greater suppression in neointimal growth."

SPIRIT III: In-segment late loss, in-stent late loss, and binary restenosis

End point XIENCE V Taxus p
In-segment late loss (mm) 0.14 0.28 <0.001 (noninferiority), 0.004 (superiority)
In-stent late loss (mm) 0.16 0.31 0.006
In-segment binary restenosis (%) 4.7 8.9 0.07
Proximal edge (%) 2.9 2.8 1.0
In-stent binary restenosis (%) 2.3 5.7 0.06
Distal edge (%) 0.9 1.3 0.65

SPIRIT III: Clinical end points

End point XIENCE V (%) Taxus (%) p
Target vessel failure 7.2 9.0 <0.0001 (noninferiority)
MACE (cardiac death, MI, ischemia-driven TLR) 4.6 8.1 0.025 (superiority)

Regarding clinical efficacy, as measured by TVF, the XIENCE V stent was statistically noninferior to the Taxus stent. MACE, which includes cardiac death, MI, and ischemia-driven TLR, was also lower with the XIENCE V stent.

"The MACE benefit in SPIRIT III was driven by a borderline statistically significant reduction in ischemia-driven target lesion revascularization, with at least the cardiac-death and myocardial-infarction numbers going in the right direction," said Stone.

Asked whether the Taxus stent is "obsolete" in light of the new data, Stone and Dr Patrick Serruys (Thoraxcenter, Rotterdam, the Netherlands), who presented data on a new fully bioabsorbable everolimus-eluting stent, also made by Abbott, were diplomatic. There will be a number of years before these new stents come full circle and can be used safely and effectively in clinical practice, said Serruys.

Stone commented that many different factors go into choosing one available drug-eluting stent over another. Clinicians will look at the positive angiographic and clinical results from this trial, but the data are available for only nine months. In contrast, others will look at the thousands of patients studied with Taxus stents, as well as their studied use in complex lesion sets.

"At the end of the day, the XIENCE V stent will be an attractive option for many clinicians but in no way does it make that Taxus stent obsolete," he said.

What does the future hold for XIENCE V?

As previously reported by heart wire , because of the fears over the risk of stent thrombosis--and whether drug-eluting stents increase the incidence of death and MI compared with bare-metal stents--clinicians, manufacturers, and regulators have been debating what these concerns might mean for next-generation stents seeking market approval.

Stone, emphasizing that he was not speaking on behalf of the FDA, said the SPIRIT III trial was designed with the FDA under previous standards, which included the ability of the stent to meet the primary and secondary end points in the study. He said he does not anticipate any new regulatory hurdles to be sprung on Abbott.

"What we have informally heard is that the companies and their devices that went through the FDA under prior guidance and guidelines are not going to be set to a new standard," he said. "That is not a formal FDA stance, although that is what I expect to happen going forward."

Dr Spencer King (Emory University School of Medicine, Atlanta, GA), who moderated the press briefing, said that at this point in time there are not enough patients or follow-up to adequately assess the long-term safety of the new stent, especially in light of the risk of stent thrombosis. However, he would like to see the new generation of stents on the market as soon as is safely possible.

"I'm not one to believe that the FDA should impose draconian measures on the new stents, which are designed to solve the problems of the previous-generation stent," he said. "You'd love to get those stents moving along, if they meet certain safety measures, but you also want much better long-term postmarket surveillance than we've had in the past."

Stone reports receiving consulting fees and honoraria from Boston Scientific and Abbott.

The complete contents of Heart wire , a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.


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