September 24, 2010 (Washington, DC) — Another day at TCT 2010 brings yet more data supporting the everolimus-eluting Xience V stent (Abbott), this time in head-to-head comparisons with the sirolimus-eluting stent Cypher (Cordis).
One study, the ISAR-TEST 4 trial, showed that the newer-generation everolimus-eluting stent had comparable clinical outcomes out to two years compared with the sirolimus-eluting stent, while the SORT-OUT 4 investigators showed the Xience V stent was statistically noninferior to Cypher for the reduction of major adverse cardiac events (MACE) at nine months.
"A lot of the times, the SORT-OUT investigators come up with the same questions and present similar data, perhaps using similar methodology," said Dr Robert Byrne (Deutsches Herzzentrum, Munich, Germany), the lead investigator of the ISAR-TEST 4 study, during a morning press conference announcing the results. "Most of the time, we come to the same conclusion. Here, in these two studies, we both fail to detect any significant clinical difference between the two stents, Cypher and Xience."
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| Dr David Cohen |
Dr David Cohen (Saint Luke's Mid America Heart Institute, Kansas City, MO), who was not part of the two European studies, said ISAR-TEST 4 and SORT-OUT 4 are the "first reasonably sized comparisons" between a first-generation sirolimus-eluting stent and a second-generation everolimus-eluting stent. While most of the data suggest Xience is superior to the Taxus paclitaxel-eluting stent, including the COMPARE and SPIRIT IV trials presented yesterday and reported by heartwire , larger studies are still needed for comparisons between Cypher and Xience.
"But I think at this point, what is starting to emerge is that the everolimus-eluting stent is a very safe stent, and we're getting more and more data from studies and relatively large populations of all-comers, which are showing very impressive results for late and very late thrombosis," said Cohen.
The Lowdown on the Two Studies
The ISAR-TEST 4 study included 1304 patients with de novo coronary artery stenosis >50% and symptoms or objective evidence of ischemia. Patients with left main disease were excluded and randomized instead to the ISAR-Left Main study, as were patients with cardiogenic shock. A second study arm, which compared a novel rapamycin (sirolimus)-coated stent with a biodegradable polymer with the permanent-polymer Cypher and Xience stents, was presented in 2009 at the European Society of Cardiology (ESC) and reported by heartwire at that time.
In the newest analysis, Byrne and colleagues report no significant differences in the combined end point of cardiac death, target vessel MI, and target lesion revascularization (TLR) at two years among patients treated with the everolimus-eluting and sirolimus-eluting stents. In terms of safety, they also observed no significant differences in definite or probable stent thrombosis between the Cypher- and Xience-treated patients.
ISAR-TEST 4: Primary End Point and Stent Thrombosis at Two Years
| End point |
Xience (n=652), % |
Cypher (n=652), % |
p |
| Cardiac death, target vessel MI, and TLR |
16.0 |
18.8 |
0.23 |
| TLR |
9.9 |
13.5 |
0.06 |
| Definite or probable stent thrombosis |
1.4 |
1.9 |
0.52 |
To heartwire , Byrne said that clinicians are aware of significant differences between first-generation stents and newer models and that analyses have also suggested that Cypher is considerably more effective, in terms of antirestenotic efficacy, and also a little bit safer than Taxus. Referring to the COMPARE and SPIRIT IV trials, which tested Taxus against the Xience stent, Byrne said such comparisons are not optimal, but this newest data from ISAR-TEST 4 and SORT-OUT 4 provide more information on just where the newest stent stands against its older counterparts.
"Before we move to fully embrace second-generation technologies, I think it's only right that we have a comparison against the standard bearer, with which we all have lots of experience and lots of data," he said. "I think our study and the SORT-OUT 4 study provide some interesting data on this issue. It seems the Xience and Cypher stents are fairly comparable in terms of their clinical efficacy."
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| Dr Stephan Windecker |
During a panel discussion of the results, Dr Stephan Windecker (Bern University Hospital, Switzerland), who presented the results of LESSON I last month at the European Society of Cardiology meeting in Stockholm, Sweden, a nonrandomized comparison of sirolimus-eluting and everolimus-eluting stents that just missed its primary end point but showed statistically significant differences in rates of MI and stent thrombosis, said the comparison between Xience and Cypher is a relevant clinical comparison. As he noted earlier, the results of LESSON I and now ISAR-TEST 4 appear counterintuitive, given that everolimus is slightly less potent than sirolimus, and it is also applied to the stent at a lower dose.
Xience in the SORT-OUT 4 Study
In a similar comparison, Dr Lisette Okkels Jensen (Odense University Hospital, Denmark) presented nine-month data from a prospective randomized study examining safety and efficacy of the sirolimus-eluting Cypher Select Plus stent and the Xience V stent in a population-based healthcare setting.
Regarding the primary end point, a composite that included cardiac death, MI, definite stent thrombosis, and target vessel revascularization (TVR), investigators report that the Xience stent was statistically noninferior to the sirolimus-eluting stent (MACE 4.9% in the Xience-treated arm and 5.3% in the Cypher-treated patients).
Speaking during the late-breaking clinical trials session, Dr Dean Kereiakes (The Christ Hospital, Cincinnati, OH) said head-to-head drug-eluting-stent trials are necessary for defining optimal care but expressed concern about the trial design of SORT-OUT 4. He specifically challenged the quadruple primary end point, one that was not used in the SORT-OUT 2 and SORT-OUT 3 trials that were used to provide end-point estimates. Moreover, he questioned the "all-comers" nature of the trial, considering that only 40% of eligible patients were enrolled and randomized and that 3% of randomized patients were not treated with the assigned study stent.
"Can a study exclude 60% of eligible patients without injecting selection bias, and does the treatment-received analysis differ from the intention-to-treat analysis?" asked Kereiakes. "This is important when dealing with low-frequency event end points."
Dr Gregg Stone (Columbia University, New York), on the other hand, said he was not as concerned about some of the issues raised. At the end of the day, he said, SORT-OUT 4 was a well-done study, and he called the results valid from the healthcare system in which it was tested.
Stone disclosed receiving research grants from Atrium, Volcano, and TherOx; consulting fees from Osprey Medical, InfraRedx, Reva Medical, Boston Scientific, Abbott Vascular, the Medicines Company, AstraZeneca, Eli Lilly, Bristol-Myers Squibb, Edwards, Evalve, Ortho McNeil, and Otsuka; holding equity in Devax; BioStar I and II funds; MedFocus I, II, and Accelerator funds; FlowCardia; MediGuide; Guided Delivery Systems; Arstasis; Micardia; and Access Closure. Cohen reports research support from MedRad, Boston Scientific, Abbott Vascular, and Edwards; consulting fees from Cordis, Medtronic, Abbott Vascular, and Boehringer Ingelheim; and speakers' fees from Eli Lilly. Kereiakes reports research support from Abbott Vascular, Amylin Pharmaceuticals, Cordis, Boston Scientific, Medtronic, and Daiichi Sankyo and consulting fees from Abbott, Boston Scientific, Eli Lilly, Medpace, and Reva Medical. Windecker reports speakers' bureau fees from Abbott, Cordis, Medtronic, Boston Scientific, and Biosensors. Jensen reports consulting for Cordis and Abbott Vascular. Byrne reports no conflicts of interest.
Heartwire from Medscape © 2010 Medscape, LLC
Cite this: Blinding Me With Xience: Everolimus-Eluting Stent Holds Its Own Against Cypher Stent - Medscape - Sep 27, 2010.
