ENDEAVOR IV: Zotarolimus- and paclitaxel-eluting stents demonstrated similar safety, efficacy
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.
