Dr Patrick Serruys

Now, in addition to those data, clinicians have yet more information to wade through as investigators presented new six-month angiographic findings for the second-generation cobalt-chromium everolimus-eluting stent. In the study, known as SPIRIT II, lead investigator Dr Patrick Serruys (Erasmus University Hospital, Rotterdam, the Netherlands) presented angiographic data showing that the Xience Vision everolimus-eluting stent was significantly better than the Taxus paclitaxel-eluting stent in preventing in-stent late loss in patients with de novo native coronary lesions.

"What was envisioned as a noninferiority trial is, as a matter of fact, a superiority trial, because the two curves for late loss separate in such a way that there is no confusion between the two populations," commented Serruys during a morning press conference announcing the positive results for the everolimus-eluting stent.

As previously noted by heartwire, stent composition and design continues, with many second-generation drug-eluting stents available outside North America doing away with stainless steel for the base stent, replacing it with alloys that maintain radiopacity and strength but permit thinner, more flexible struts. The everolimus-eluting stent, made by Abbott, has already gained CE mark approval in Europe.

In this noninferiority study, investigators randomized 300 patients in a 2:1 ratio to the everolimus-eluting stent or the Taxus stent. Patients included in the study were relatively easy to treat and included in the study with de novo lesions <28 mm and with a target lesion reference diameter >2.5 and <4.25 mm. Approximately 25% in each study arm had diabetes mellitus, with 5% of the everolimus-treated patients and 7% of the paclitaxel-treated patients having insulin-dependent diabetes. The primary end point of the study was in-stent late loss measured at 180 days.

At six months, in-stent late loss was significantly lower in those treated with the everolimus-eluting stent. In-stent diameter stenosis was also less in patients treated with the Xience Vision stent. There was no significant difference in MACE rates, a composite end point of cardiac death, MI, and ischemia-driven target lesion revascularization (TLR).

Despite the positive data, no presentation on drug-eluting stents could escape the shadow cast by two meta-analyses presented earlier in the meeting. Both meta-analyses combined all of the Cordis/J&J-sponsored Cypher randomized trials, as well as the Boston Scientific-sponsored Taxus program. As previously reported by heartwire, one of these studies found an increased incidence of death and Q-wave MI with the Cypher stent and a trend toward increased death/Q-wave myocardial infarction with Taxus. The second found no differences in cardiac mortality but an increase in noncardiac mortality, again with the Cypher stent.

Asked during the press conference if the lower late loss might not be the Achilles heal of the SPIRIT II study, given that Cypher had lower late loss than the Taxus stent and now was showing a possible late risk of cardiac events, Serruys stressed that a delicate equilibrium is at play.

"It's a balance between the neointimal hyperplasia and the quality of the endothelium. This will, of course, be the topic of research and debate for the next few years. It's clear that we have to find the right balance," said Serruys. He suggested that late loss between 0.2 and 0.3 mm would be beneficial for neointimal growth. Offsetting this, however, there is also a need for quality endothelium. "If we don't have good endothelium, we'll also be in trouble," he said.

Taking up the issue of late loss as an end point, Dr Robert Harrington (Duke University Medical Center, Durham, NC), the discussant of the SPIRIT II trial, said previous studies have shown late loss to be a consistent measure of neointimal hyperplasia, which is the underpinning of restenosis in the stented population. Late loss, noted Harrington, is currently being used as a biomarker to increase the power in comparator trials of drug-eluting stents.

Now the question is, do we need to worry about the thrombosis indefinitely?

"But what I would submit to you is that what we really need to know about the technology is some of what is starting to be discussed at this meeting," said Harrington. "That is, there is an emerging, and very passionate, controversy over drug-eluting stents in that perhaps, and I stress the word perhaps, they may increase the risk of late cardiac events."

Harrington noted that in autopsied patients with a drug-eluting stent, investigators have observed less neointimal hyperplasia compared with those treated with a bare-metal stent. There is also more fibrin deposition in the drug-eluting-stent patients, suggesting less healing, as well as less strut endothelialization. The reason this is so important is that many patients stop dual antiplatelet therapy too early, often before 30 days, significantly increasing their risk of MI.

"So I ask us as a community to consider these trade-offs of restenosis vs thrombosis and note that when angioplasty first came, we worried about thrombotic events for 24 hours as a trade-off of restenosis. When we moved to bare-metal stents we now worried about the trade-off of thrombosis for seven to 14 days. Now the question is, do we need to worry about the thrombosis indefinitely?"