At the recent World Congress of Cardiology conference in Barcelona, Spain, Professor Patrick W Serruys, of the Thoraxcenter, Erasmus University Hospital, Rotterdam, revealed six-month results of Abbott's 300-patient randomised, single-blind, prospective SPIRIT II clinical trial.
The SPIRIT II study evaluated Abbott's Xience V (marketed by Boston Scientific as Promus) everolimus-eluting coronary stent system versus Boston's Taxus paclitaxel-eluting coronary stent system. Attendees were shown that Xience V demonstrated superiority compared to the Taxus stent system, with respect to the study's primary endpoint, which was angiographic in-stent late loss at six months (0.11 +/- 0.27mm for Xience V vs. 0.36 +/- 0.39mm for Taxus, p<0.0001).
In SPIRIT II non-inferiority study, investigators randomised 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 <28mm and with a target lesion reference diameter >2.5mm and <4.25mm. 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 revascularisation (TLR).
According to Serruys, secondary endpoints also demonstrated positive results for the Xience V stent system. Such results included a statistically significant reduction in percent diameter stenosis from 21% for Taxus to 16% for Xience V (p<0.001). The in-stent angiographic binary restenosis rate for Xience V was 1.3% compared to 3.5% for the Taxus control. The six-month major adverse cardiac events (MACE) rate for the Xience V stent was 2.7%, vs. 6.5% for the Taxus stent. As defined in SPIRIT II, the MACE rate includes any deaths, heart attacks or clinically driven target lesion revascularisations within the six-month period. The study also showed a stent thrombosis rate for Xience V of 0.5% (n=1) at six months compared to 1.3% (n=1) for that of Taxus. The device and procedural success rates for the Xience V stent system were 98.8 and 99.1%, respectively.
"The excellent results demonstrate that in this trial, the Xience V stent was not only non-inferior but was also superior to the Taxus stent, and confirm the positive results from the SPIRIT FIRST study," said Serruys. "The stent system's impressive safety and efficacy data, combined with its highly deliverable platform, will make Xience V an attractive new drug-eluting stent for physicians and patients in Europe."
After presenting the data, Serruys stated "While Xience met the trial's primary non- inferiority end-point of in-stent late loss, larger confirmatory trials will be required to validate the safety and effectiveness shown to date."
Despite the positive data, also presented at the meeting were two meta-analysis combining all of the Cordis/J&J-sponsored Cypher randomised trials, as well as the Boston Scientific-sponsored Taxus program. It was shown that 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 MI with Taxus. The second found no differences in cardiac mortality but an increase in non-cardiac 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," Surreys suggested that late loss between 0.2 and 0.3mm 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 warned.
Thrombosis concerns
Mentioning 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 DES.
"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 explained that in autopsied patients with a DES, investigators have observed less neointimal hyperplasia compared with those treated with a bare metal stent. There is also more fibrin deposition in the DES patients, suggesting less healing, as well as less strut endothelialisation. 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?"
Meanwhile, Boston Scientific welcomed the results of the trial, which according to the company, reaffirmed the safety and efficacy of the Taxus stent. Designed as a non-inferiority trial, SPIRIT II is the first head-to-head randomised trial of two different drug-eluting stents in which one company will market both products
"SPIRIT II adds to the extensive body of clinical evidence from randomised trials that reinforce the excellent safety and efficacy of the Taxus Stent System, and provides solid traction for growth of the Promus Stent," said Jeff Goodman, president of Boston Scientific International.
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