ZEST: 3 Stents Go Head-to-Head-to-Head

ZEST: 3 Stents Go Head-to-Head-to-Head
Real World Comparison of Sirolimus, Paclitaxel and
Zotarolimus-Eluting Stents in 2,640 Patients

related stories:
Drug-Eluting Stent Center

external sites:
Medtronic, Inc.

Taxus Liberte, Endeavor and Cypher Stents

Taxus Liberte (L), Endeavor (R)
and Cypher (background) stents

March 29, 2009 -- Orlando, Florida -- The results of ZEST, a large scale randomized multi-center trial of all comers were presented this morning to the i2 Summit at ACC.09 by Dr. Seung-Jung Park of Asan Medical Center in South Korea. The goal of the trial was to evaluate paclitaxel- and sirolimus-eluting stents compared with zotarolimus-eluting stents in patients with coronary artery disease.

Somewhat surprisingly, the sirolimus-eluting CYPHER stent, the oldest drug-eluting stent in use, scored quite well, which pleased its manufacturer Cordis/Johnson & Johnson.

Also pleased was Medtronic, co-sponsor of the trial, because the purpose of the trial was to show non-inferiority of their Endeavor zotarolimus-eluting stent with the Cypher -- and to show superiority to Boston Scientific's widely-utilized Taxus Liberte paclitaxel-eluting stent. The Endeavor succeeded on both counts. Abbott Vascular's XIENCE V stent was not part of this study.

For the ZEST study, 2,640 patients were randomized equally across the three platforms. Almost half the patients had multivessel disease; more than half presented with acute coronary syndrome. The patient population included significant numbers of long lesions and bifurcation lesions. Intravascular ultrasound was used in 41%.

At 12 months, the primary outcome of death, myocardial infarction, or target vessel revascularization (MACE) had occurred in 10.1% of the zotarolimus group, 8.3% of the sirolimus group, and 14.2% of the paclitaxel group (p = 0.25 for zotarolimus vs. sirolimus, p < 0.0003 for zotarolimus vs. paclitaxel). Respectively for zotarolimus, sirolimus, and paclitaxel: death was 0.7%, 0.8%, and 1.1%, myocardial infarction was 5.3%, 6.3%, and 7.0%, target lesion revascularization was 4.9%, 1.4%, and 7.5%. Stent thrombosis was 0.5%, 0%, and 0.7% -- with no statistically significant difference in the three stents.

The Endeavor and CYPHER, while varying slightly in the measures, had no statistically significant differences for the primary endpoint of MACE, whereas the Taxus Liberte showed statistically higher MACE. The CYPHER did require less revascularization (kept the artery open better) than the Taxus, and the Endeavor fell in-between. Joseph McGrath, a spokesperson for Medtronic stated:

"Data presented for the first time to today from the ZEST study showed that the Endeavor Drug-Eluting Stent (DES) was non-inferior to the Cypher DES while also being associated with a statistically significant 29% reduction in the composite primary endpoint of Death, Myocardial Infarction (MI) and in ischemia-driven Target Vessel Revascularization (TVR), when compared to the Taxus Liberte DES at one year.

"Boston Scientific's Taxus Liberte DES is currently the market leader in the United States, yet it was shown in this randomized controlled trial to be associated with a 25% increase in Death and MI, and a 32% increase in the need for repeat revascularization when compared to the next-generation Endeavor DES from Medtronic. These increases drove a statistically-significant 29% increase in the primary endpoint at one year (P=0.0003)."

In a video clip on the ACC web site CardioSource, Dr. Seung-Jung Park explained that, although the CYPHER and Endeavor stents performed similarly, and the CYPHER trended better in certain areas, the underlying stent structures of the two stents differ, the Endeavor being a second-generation DES with thinner struts and a different polymer. He concluded that a decision about which stent to use should take into account anatomy and lesion characteristics, as well as the results from the ZEST Trial.

Reported by Burt Cohen, March 29, 2009