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ENDEAVOR IV: Zotarolimus- and paclitaxel-eluting stents demonstrated similar safety, efficacy
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The zotarolimus- and paclitaxel-eluting stents had similar safety and efficacy at one year in patients with coronary artery disease.
Researchers from the ENDEAVOR IV trial enrolled 1,548 patients with single de novo coronary lesions and randomly assigned them at a 1:1 ratio to either a zotarolimus-eluting stent (Endeavor, Medtronic; n=773) or a paclitaxel-eluting stent (Taxus, Boston Scientific; n=775). The primary study endpoint was noninferiority of target vessel failure at nine months defined as cardiac death, MI or target lesion revascularization.
According to the results, target vessel failure at nine months was similar between the zotarolimus and the paclitaxel groups (6.6% vs. 7.1%; P≤.001 for noninferiority). The researchers reported no significant differences at nine and 12 months between study groups for death, cardiac death, MI and major adverse cardiac events. There were also no significant differences at nine and 12 months in overall clinically driven target lesion revascularization or target vessel revascularization. There were fewer periprocedural non–Q-wave MI with the zotarolimus-eluting stent vs. the paclitaxel-eluting stent (0.5% vs. 2.2%; P=.007).
“The ENDEAVOR IV trial should be viewed as a component of the larger comprehensive assessment of the new Endeavor zotarolimus-eluting stent,” the researchers concluded. “Compared with the well-characterized paclitaxel-eluting stent, findings from this randomized trial indicate that in single de novo coronary lesions, the Endeavor zotarolimus-eluting stent has improved periprocedural safety, similar 12-month clinical safety and efficacy outcomes, and despite more frequent angiographic restenosis, similar clinical repeat revascularization events.”
In an accompanying editorial, E. Magnus Ohman, MD, and Robert M. Califf, MD, both of the Duke Heart Center in Durham, N.C., noted that the concept of noninferiority, despite being common for measuring the comparative effectiveness of treatments in many clinical trials, should be examined closely and carefully by clinicians in various clinical scenarios.
“Our belief is that the best approach to this conundrum is to have more appropriately sized clinical endpoint-based investigation to better capture the overall intent of comparative research, namely improvement in significant clinical endpoints such as death, MI and the need for subsequent revascularization,” they wrote. “Whereas these trials should be designed to either capture superiority or true equivalence, the complexity of the possible findings should not be dismissed because rational and intelligent people often will value different parts of a composite endpoint in different ways.” – by Eric Raible
The results are encouraging but raise additional questions. Although a less aggressive cellular attack may enhance early healing and limit adverse events such as late stent thrombosis, a potentially higher risk for late revascularization because of an increase in late loss will have to be coupled with an ischemic/symptom-driven indication for follow-up angiography to avoid an overzealous oculostenotic reflex.
Furthermore, although a small increased risk for early stent thrombosis for the zotarolimus-eluting stent may be perhaps explained by “bad luck” based on adverse anatomic results of these select patients, there is no evidence that similar adverse anatomic outcomes may have occurred in some of the paclitaxel-eluting stent patients without a similar rate of early stent thrombosis.
Lastly, these were low- to medium-risk patients with relatively short follow-up, so these results do not apply universally to all patient populations — without further studies and longer follow-up. That said, there is a clear need to continue to explore new approaches in terms of drugs, polymers and stent platforms to refine drug-eluting stents, and the zotarolimus-eluting stent represents an important step in this ongoing process. The data from Leon and colleagues in this trial showing noninferiority for the zotarolimus-eluting stent platform are critical to our growing understanding of drug-eluting stent selection.
– George Vetrovec, MD
Cardiology
Today Editorial Board
Leon MB. J Am Coll Cardiol. 2010;55:543-554.