Chicago, IL - One-year results from the SPIRIT III trial comparing the Xience V everolimus-eluting stent with the Taxus paclitaxel-eluting stent suggest that the yet-to-be approved Xience may offer an edge, at least in the kinds of low-risk patients enrolled in the study [1]. In the trial, late loss and major adverse cardiac events (MACE) were significantly lower in Xience-treated patients than in subjects who received the Taxus stent, while target vessel failure was "noninferior." The one-year results are now published in the April 22, 2008 issue of the Journal of the American Medical Association.

Experts enthusiastic about the results nevertheless emphasize that longer-term outcomes, in a broader patient population, are needed to confirm that the newer stent offers enduring clinical benefits over its predecessor.

"The real question is, how about off-label lesions and how about follow-up out to two, three, four, or five years?" lead investigator Dr Gregg Stone (Columbia University, New York, NY) asked in an interview with heartwire. "Do the differences in events continue to spread, or do they get narrower? How about late stent thrombosis compared with earlier stent thrombosis? With one-year follow-up for on-label lesions, I'm very confident that this stent does represent a significant advance and improved options for patients with CAD. And we have to wait until we have more experience with more complex lesions and longer-term follow-up to know whether this should be a total replacement of other [drug-eluting stents] DES."

Similarly, Dr Manesh R Patel (Duke Clinical Research Institute, Durham, NC), who with Dr David R Holmes (Mayo Clinic, Rochester, MN) wrote the editorial accompanying the published SPIRIT III results [2], called the findings "encouraging."

"I think if the FDA approves this—and that's yet to be determined—patients who fit the criteria for this trial will likely benefit from this stent; however, we don't know the long-term effects yet and we certainly don't know how patients with complex lesions or many other types of patient scenarios that aren't represented in this trial will do with this stent," Patel told heartwire. "Unfortunately, there isn't a straightforward message here. The message is that this is a small incremental step forward and hopefully it will be a bigger one as time goes on."

As previously reported by heartwire, an FDA advisory panel recommended approval of the device last November; it is already on the market in Europe. Abbott acquired the rights to the Xience V in an agreement with Boston Scientific, which bought out the original Xience developer, Guidant, in 2006. Under the terms of the agreement, Boston Scientific has its own, identical version of the Xience V, dubbed the "Promus" stent, for which it pays a royalty to Abbott. Both stents would enter the US market simultaneously if approved—something market watchers predict will likely happen in the next few months.

Stone, who first presented the SPIRIT III results at the TCT 2007 meeting, told heartwire that two-year results will be presented at the upcoming EuroPCR meeting in Barcelona. He highlighted design characteristics of the Xience—thinner struts; a thin, nonreactive polymer; and a drug with similar potency to sirolimus—as key reasons not only for the reduced late loss at nine months, fewer repeat procedures at one year, and fewer periprocedural MIs, but also as factors that may ensure the stent also performs better over time. "This is the first head-to-head DES trial in a large pivotal study of any DES vs either Taxus or Cypher that has shown a reduction in MACE," he said. "And now this is the second trial in a row to show it—it was also shown in SPIRIT II."

Stone was referring to one-year results from SPIRIT II, which showed a statistically significant reduction in MACE at 12 months with the Xience vs the Taxus. At both six months and two years, however, there was only a trend toward reduced MACE with the Xience that did not reach statistical significance. SPIRIT II was underpowered to show a reduction in MACE, Stone acknowledged.

The SPIRIT III investigators emphasize that while stent thrombosis rates were no different between the two stents, according to either study protocol definitions or the Academic Research Consortium definitions, this is an issue that will need to be studied closely in subsequent studies and ongoing follow-up. Stone expressed optimism that the thin-strut design and swifter reendothelialization may help with this. In work by Dr Renu Virmani's group (CVPath Institute, Gaithersburg, MD), using a 14-day rabbit iliac-aorta model, endothelialization occurred more rapidly with the Xience than with the Endeavor, Cypher, or Taxus stents, Stone noted. "What 14 days in a rabbit means to a human over two years or three years, etc, is unknown," he observed. "Obviously, we need tens of thousands of humans to know whether this translates into less stent thrombosis."

In their editorial, Patel and Holmes also emphasize the need for information on how the stent would perform in a broader population and whether late stent thrombosis will be a problem for the new DES long-term. So far, what SPIRIT III contributes is proof that the stent "does what it is intended to do technically, ie, reduce a measure of restenosis (late loss) while being noninferior for target vessel failure," Patel and Holmes write. More results from randomized trials, and not just registries, will be needed to answer these questions, they emphasize.

And while waiting for those answers, given the pervasive use of already-approved DES for "off-label" indications, clinicians will likely embrace the Xience, and not just for patients similar to the SPIRIT III population, Patel acknowledged. "For those patients where we have to apply a DES in an off-label indication or we think a DES is required, I think this will certainly play an important role in our armamentarium," Patel commented.