ORLANDO, Fla.—A large, randomized, controlled multicenter study in Korea found that the second-generation Endeavor drug-eluting stent (DES) was not inferior to the first-generation Cypher DES but was superior in several ways to the first-generation Taxus DES, according to research presented during the i2 Summit at the American College of Cardiology (ACC) 58th annual scientific session.
The Zotarolimus-Eluting Stent Versus Sirolimus-Eluting Stent and PacliTaxel-Eluting Stent for Coronary Lesions (ZEST) trial tracked combined rates of death, MI and repeat procedures in patients treated with Endeavor (Medtronic), Cypher (Cordis) and Taxus (Boston Scientific) DES. The sirolimus- and paclitaxel-eluting stents (Cypher and Taxus, respectively) have been very effective in preventing in-stent restenosis compared to bare-metal stents (BMS), but stent thrombosis has been a problem with those stents. In theory, because Endeavor, which elutes zotarolimus, is coated with a biocompatible phosphorylcholine (PC) polymer, it promotes healing of the artery wall, lessening the chances of late stent thrombosis, said lead investigator Seung-Jung Park, MD, from the Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
"Although second-generation drug-eluting stents may be theoretically less prone to thrombosis, large randomized trials comparing first- and second-generation devices in ‘all-comers' have been limited," Park said.
Park and colleagues from 19 university hospitals in Korea equally randomized 2,640 patients to the three DES. Patients were typical of those treated by interventional cardiologists every day. The mean age was 62 years, and 67 percent of the patients were men. Overall, 29 percent of the patients had diabetes, 55 percent were treated for an acute coronary syndrome, 9 percent had previously undergone coronary angioplasty, and 47 percent had multivessel disease. Some 74 percent of lesions were considered to be of intermediate-to-high severity or complexity (type B2/C). In addition, 55 percent of lesions were diffuse and long (greater than 20 mm), 14 percent were situated at an arterial branchpoint, and 7 percent were situated in the opening of an artery.
Researchers found Endeavor non-inferior to Cypher, while also being associated with a statistically significant 29 percent reduction in the composite primary endpoint of death, MI and in ischemia-driven target vessel revascularization (TVR), when compared to the Taxus at one year.
At one year, the Cypher had a zero percent rate of stent thrombosis (ARC definite criteria), while Endeavor's rate was 0.5 percent and Taxus had a 0.7 percent rate. The numbers were similar for ARC definite or probable criteria and ARC any criteria.
There were statistically significant differences in rates of TVR and target lesion revascularization (TLR). TVR was 5.2 percent (Endeavor), 1.8 percent (Cypher) and 7.6 percent (Taxus). TLR was 4.9 percent, 1.4 percent and 7.5 percent, respectively.
Results of quantitative coronary analysis will be reported in the final study, Park said. He concluded that compared with first-generation stents, the use of Endeavor results in similar major adverse cardiac events with reference to Cypher, but in fewer major adverse cardiac events with reference to Tasux. Endeavor showed a trend toward lower rates of death or MI compared with the two other stents.
Joe McGrath, a spokesperson for Medtronic, makers of Endeavor and sponsor of the trial, said, "The Taxus Liberte is currently the market leader in the United States. Yet it was shown in this randomized controlled trial to be associated with a 25 percent increase in death and MI, and a 32 percent increase in the need for repeat revascularization when compared to the next-generation Endeavor. These increases drove a statistically significant 29 percent increase in the primary endpoint at one year."
In his commentary on the study, Stephan Windecker, MD, from the department of cardiology at Bern University Hospital in Switzerland, praised the trial for its high quality, its large size and for taking all comers. "The broad inclusion criteria enhance its results," he said.