March 31, 2009 (Orlando, Florida) — The largest study to date comparing first- and newer-generation drug-eluting stents (DES) in a real-world environment has shown encouraging results for the new zotarolimus-eluting Endeavor (Medtronic)--launched a year ago in the US and approved just yesterday in Japan --as well as the older sirolimus-eluting Cypher (Cordis/Johnson & Johnson).
But the data for the Taxus Liberté, Boston Scientific's newer paclitaxel-eluting DES, were disappointing. Dr Seung-Jung Park (Asan Medical Center, Seoul, South Korea) reported the findings of the 2500-patient, one-year, noninferiority trial ZEST here during a late-breaking clinical-trials session at the American College of Cardiology 2009 Scientific Sessions.
Trial discussant Dr Stephan Windecker (University Hospital, Berne, Switzerland) applauded Park and colleagues for ZEST "and its broad inclusion criteria, which enhance its generalizability to clinical practice. This is a high-quality trial addressing a relevant clinical question--namely, differences among first- and newer-generation DES. This study clearly shows that Endeavor is less effective than Cypher but at least as effective as Taxus." With respect to safety, there were no differences in mortality between the three; there was a similar incidence of MI between Endeavor and Cypher, but a lower rate of MI seen with Endeavor compared with Taxus.
In an interview with heartwire , Dr Mark Turco (Washington Adventist Hospital, Tacoma Park, MD), who was not involved with this study, said interventionalists could be reassured by the ZEST data: "If we look at how all three DES performed in a very complex patient population--this was all-comers, with many lesions that would be considered off-label use in the US, such as long lesions, calcific lesions, and bifurcation disease--we should feel good about the first- and now the second-generation DES."
The Taxus Liberté efficacy results were certainly not as good as we've seen. . . . The question is whether this is an aberration with this particular . . . trial or . . . something we need to look at.
But he conceded that the ZEST data were a little disappointing for Taxus Liberté: "The Taxus Liberté efficacy results were certainly not as good as we've seen in the ATLAS trial and the ARRIVE real-world registries. The question is whether this is an aberration with this particular Korean trial or whether this is truly something we need to look at. It is a bit discordant with the other data that we have on Taxus Liberté."
Turco said he was buoyed by the "continued good efficacy of Cypher seen in ZEST and the consistency of data with Endeavor, which is exactly what we have seen in other trials. We saw especially low rates of MI with Endeavor in this trial. Also, a [target lesion revascularization] TLR rate of 4.9% with angiographic follow-up in a highly complex patient subset is good evidence that Endeavor performed well. "
He added: "There's a lot of good to learn from this. There are those who say, 'Gee, these are Korean data and really not applicable to what we do in the US,' but I would hasten to add that this is not the case."
Longer-Term Data Needed to Properly Judge Stent-Thrombosis Rates With Endeavor
Park said that Endeavor, as a second-generation DES, is theoretically less prone to stent thrombosis, but currently available large randomized trials comparing first- and second-generation DES in all comers have been limited.
He and his colleagues included all comers requiring PCI with a stent for coronary lesions at 19 centers in Korea, with 2640 patients randomized equally across three platforms. Almost half the patients had multivessel disease, and more than half presented with acute coronary syndrome. The patient population included significant numbers of long lesions and bifurcation lesions, and more than 30% were diabetic. Intravascular ultrasound was used to guide procedures in 41% of cases, and angiographic follow-up was performed at one year.
There was no difference for the primary end point of MACE--death from any cause, MI, or ischemic driven target vessel revascularization [TVR]--between Endeavor and Cypher. But Taxus Liberté showed statistically higher MACE. The primary end point occurred in 10.1% of the Endeavor group, 8.3% of the Cypher group, and 14.2% of the Taxus Liberté arm (p=0.25 for Endeavor vs Cypher and p<0.0003 for Endeavor vs Taxus Liberté).
The Cypher did require less revascularization than the Taxus Liberté, and the Endeavor fell in between.
Major Clinical End Points in ZEST at One Year
|End point||Endeavor, n=880 (%)||Cypher, n=880 (%)||Taxus Liberté, n=880 (%)||p|
Stent thrombosis at one year was 0.5%, 0%, and 0.7%, for Endeavor, Cypher, and Taxus Liberté, respectively, with no significant difference between the three.
Turco told heartwire : "The stent-thrombosis rate with Endeavor is pretty consistent with where it has been in all the other trials. Where Endeavor has really won out from the standpoint of stent thrombosis is beyond one year. It will be interesting as we get longer-term follow-up on these patients to see what happens to the curves and to see whether Endeavor remains flat and the other two increase."
Windecker had similar views. He said that longer-term follow-up was needed to better judge this outcome: "I would encourage you to await the PROTECT trial for a definitive answer regarding the long-term safety and very late stent thrombosis of Endeavor."
Lessons to Be Learned From the Asian Countries?
In a panel discussion following the presentation of the ZEST results, debate centered on whether follow-up angiograms could have influenced the results. Windecker said that while this was possible, "if we look at the relative risk reduction in those patients who had angiographic follow-up vs those who didn't, in general, the relative risk reduction is the same, so I don't consider it a major disadvantage of this trial."
Turco said more intravascular-ultrasound [IVUS]–driven procedures are performed in countries like Korea and Japan, and "we in the US probably do need to have a higher utilization of IVUS to obtain some of the excellent results that countries like these achieve.
"Yes, we can say the Koreans are very meticulous operators, and that may not be consistent with what's happening in the US, but that said, the data here are very similar to the numbers we saw with Cypher and Endeavor in SORT-OUT 3 and the E5 registry, so it's too easy to say this is a Korean trial and it doesn't represent what's going on in the US."
ZEST was supported by Medtronic. Windecker receives consulting fees from all manufacturers involved in this trial. Turco is a consultant for Boston Scientific and Medtronic and receives research support from Boston Scientific.
Medtronic Inc. Medtronic receives regulatory approval for Endeavor drug-eluting coronary stent in Japan [press release]. March 30, 2009. Available here.
Heartwire from Medscape © 2009 Medscape, LLC
Cite this: ACC 2009: Cypher and Endeavor Trump Taxus Liberte in ZEST Trial - Medscape - Mar 31, 2009.