ENDEAVOR IV finds zotarolimus- has similar outcomes to paclitaxel-eluting stent
MedWire News: Results from the ENDEAVOR IV trial demonstrate that the second-generation zotarolimus-eluting stent (ZES) has similar safety and efficacy to the paclitaxel-eluting stent (PES) at 1 year of follow-up, report researchers in the Journal of the American College of Cardiology.
The study found no differences at 1 year between ZES and PES in rates of cardiac death, myocardial infarction (MI), target vessel revascularization (TVR), or stent thrombosis. Although 8-month angiographic results indicated a higher rate of in-segment restenosis with ZES, target lesion revascularization (TLR) was similar with ZES and PES at 12 months.
Safety concerns over drug-eluting stents (DES), mainly relating to a small increase in late (beyond 1 year) stent thrombosis compared with bare-metal stents, have led to a shift in treatment to include extended dual antiplatelet therapy and continued efforts to refine features of these stents.
Most observers agree that impaired early and late healing responses, perhaps associated with certain biostable polymers, are at play. The ZES combines the rapid elution profile of the antiproliferative drug zotarolimus with a thin, biocompatible phosphorylcholine polymer placed on a cobalt alloy thin-strut stent, and has shown promising experimental and early clinical results, explain Martin Leon (Columbia University, New York, USA) and co-investigators.
In the ENDEAVOR (Randomized Comparison of Zotarolimus-Eluting and Paclitaxel-Eluting Stents in Patients with Coronary Artery Disease) IV trial, the researchers randomly assigned 1548 patients with single de novo lesions to receive ZES (n=773) or PES (n=775).
The primary endpoint of target vessel failure (cardiac death, MI, or TVR) at 9 months occurred in 6.6% of patients receiving ZES and 7.1% of those receiving PES, demonstrating non-inferiority of ZES to PES (p≤0.001).
However, the secondary endpoint of late in-segment lumen loss, measured by quantitative intravascular ultrasound imaging in 164 patients in each treatment group at 8 months, was not met. Average neointimal volume was significantly higher at 24.14 mm3 in the ZES group versus 14.88 mm3 for PES patients (p=0.002) and percent volume obstruction was 15.72 for ZES versus 9.88 for PES (p<0.001).
Nevertheless, despite the “less robust reduction in intimal hyperplasia,” the authors say that the clinical expression of restenosis was no different between the two study cohorts after 9- and 12-month follow-up, with similar rates of both TLR and TVR. For instance, at 1 year Kaplan-Meir analysis showed the cumulative rate of TVR in the ZES versus PES group was 6.2% versus 6.8%, respectively (hazard ratio=0.92, 95% CI: 0.62–1.36).
At 30 days, there were fewer periprocedural non–Q-wave MIs in patients receiving ZES versus patients receiving PES (0.5% vs 2.2%, p=0.007), but there were no significant differences at 9 months or 1 year in individual safety endpoints such as cardiac death (0.4% vs 0.3% and 0.5% vs 0.5%, respectively) or MI (1.4% vs 2.4% and 1.6% vs 2.7%), or for cardiac death or MI combined (2.6% vs 3.1% at 1 year; HR=0.66, 95% CI: 0.35–1.25).
In addition, there were no statistically significant differences in stent thrombosis between ZES and PES groups. Leon and team point out that there was a trend toward higher protocol definition and Academic Research Consortium (ARC; definite or probable) definition stent thrombosis with ZES at both 9 and 12 months. But they say three of the total seven ARC defined stent thrombosis cases occurred before 30 days and were related to procedural problems or unplanned surgery, while three of four cases between 30 days and 6 months occurred after withdrawal of clopidogrel, of which one patient had also undergone unplanned surgery.
Noting that the ENDEAVOR IV trial should be viewed as a component of the larger comprehensive assessment of the ZES stent, the authors conclude: “Compared with the well-characterized PES, findings from this randomized trial indicate that in single de novo coronary lesions, the Endeavor ZES has improved periprocedural safety, similar 12-month clinical safety and efficacy outcomes, and despite more frequent angiographic restenosis, similar clinical repeat revascularization events.”
Discussing the challenges of establishing “similarity” between newer second- and older first-generation DES, Magnus Ohman and Robert Califf (Duke Medical Center, Durham, North Carolina, USA) said in an accompanying article that, “in statistical terms, the most prudent conclusion is that ZES is indeed non-inferior and that a reduction in [periprocedural] MI observed is of interest but can only be hypothesis-generating and should be tested in another trial.”
They added the cautionary note that the combined trial experience to date “suggests that ZES may indeed have a positive effect on periprocedural MI but an untoward effect on late segment loss and/or restenosis.”
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By Caroline Price