Zotarolimus-Eluting stent Non-Inferior to the Paclitaxel-Eluting Stent in Target Vessel Failure, but a Trend Toward Higher Stent Thrombosis is Observed with Zotarolimus: Results of ENDEAVOR 4 Trial

October 22, 2007 by C. Michael Gibson, M.S., M.D.

Washington DC: In the recent ENDEAVOR 3 trial, the zotarolimus-eluting stent was associated with significantly greater late lumen loss on angiography when compared with the sirolimus-eluting stent. The occurrence of greater intimal hyperplasia was actually welcomed by some interventional cardiologists who thought that greater intimal hyperplasia covering stent struts might reduce the risk of stent thrombosis. Similar results were reported in comparison to the Paclitaxel eluting stent today in the ENDEAVOR 4 study, with an unexpected twist: there was a trend toward higher rates of stent thrombosis with the zotarolimus stent.

ENDEAVOR 4 compared the Endeavor zotarolimus-eluting stent (n = 773) to the Taxus paclitaxel-eluting stent (n = 775) in patients undergoing PCI of a single de novo coronary lesions. The primary pre-specified endpoint of the study was non-inferiority in the risk of target vessel failure (TVF or clinical restenosis) at 9 months. In a subset of 279 patients, repeat angiography was performed at 8 months to evaluate angiographic restenosis.

The primary endpoint of target vessel failure (TVF) at 9 months met the pre-specified criteria for non-inferiority (6.6% for zotarolimus vs 7.2% for paclitaxel, p < 0.001 for non-inferiority). When the results were evaluated later, at 1 year, TVF was observed in 7.7% of zotarolimus patients and 9.4% of paclitaxel patients.

In the 279 patients who underwent repeat angiography at 8 months, the zotarolimus eluting stent was associated with greater late lumen loss than the paclitaxel eluting stent both when measures of in-stent restenosis (0.67 mm vs. 0.42 mm respectively, p < 0.001) and in-segment restenosis were compared (0.36 mm vs. 0.23 mm, p = 0.023). Consistent with the results for late lumen loss, the follow-up in-stent percent diameter stenosis was tighter for the zotarolimus elutig stent (26.4% vs. 16.1%, p < 0.001). When the traditional definition of binary stenosis was applied, the rates tended to be higher for the zotarolimus group compared with the paclitaxel group (13.3% vs 6.7% respectively, p = 0.075).

Overall stent thrombosis by 1 year trended higher in the zotarolimus group (0.8% vs. 0.1%, p = 0.124), with 3 of the 6 stent thrombosis events in the zotarolimus group occurring by 30 days and the remaining 3 events occurring at day 83, 145 and 171. Despite this trend toward higher rates of stent thrombosis, there was no difference in mortality (there were 1.1% deaths in each group) or myocardial infarction (1.6% vs. 2.6%, respectively, p = 0.21). A longer follow-up is needed to more appropriately evaluate the relative risk of stent thrombosis in the two groups.