Randomized, Controlled Trial of the Medtronic Endeavor Drug-Eluting Coronary Stent System Versus the Taxus Paclitaxel-Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions - ENDEAVOR IV

Feb 01, 2010
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Trial Sponsor:
Medtronic, Inc.
Date Presented:
01/01/2008
Date Published:
01/01/2009
Date Updated:
02/01/2010
Original Posted Date:
02/01/2010
References

Description:

The goal of the trial was to evaluate treatment with the Endeavor zotarolimus-eluting stent (ZES) compared with treatment with the Taxus paclitaxel-eluting stent (PES) among patients with single de novo coronary lesions.

Hypothesis:

Treatment with ZES would be noninferior to treatment with PES in patients with a single de novo coronary lesion.

Study Design

Study Design:

Patients Enrolled: 1,548
Mean Follow Up: 36 months
Mean Patient Age: 63.5 years
Female: 32

Patient Populations:

  • Single de novo lesion in native coronary artery with a vessel diameter 2.5-3.5 mm

Primary Endpoints:

  • Target vessel failure at 9 months
  • Stent thrombosis (Academic Research Consortium [ARC] definition)

Drug/Procedures Used:

Patients were randomized to percutaneous coronary intervention (PCI) with a ZES (n = 773) or a PES (n = 775). Predilatation was required. The dose of zotarolimus was 10 µg per mm stent length. Repeat angiographic follow-up was performed at 8 months in a subset of patients (n = 279).

Principal Findings:

Baseline clinical characteristics were well balanced between groups. Prior myocardial infarction (MI) was present in 22%. Treated lesion was the left anterior descending in 42% of patients. The mean baseline percent diameter stenosis was 65%.

In the angiographic subgroup (n = 279), late loss was greater in the ZES group than the PES group both in-stent (0.67 mm vs. 0.42 mm, p

The primary endpoint of target vessel failure at 9 months met the noninferiority margin of difference, with an event rate of 6.6% in the ZES group and 7.1% in the PES group (p

At 1 year, target vessel failure had occurred in 7.7% of the ZES group and 9.6% in the PES group, and major adverse cardiac events (MACE) in 6.5% and 6.7%, respectively. Among the individual endpoints, there were few deaths (1.1% in each group) or MIs (1.6% vs. 2.7%, respectively, p = 0.16). Target vessel revascularization was similar between groups (6.2% vs. 6.8%, p = 0.68). Overall stent thrombosis by 1 year trended higher in the ZES group (0.8% vs. 0.1%, p = 0.124), with three of the six stent thrombosis events in the ZES group occurring by 30 days and the remaining three events occurring at days 83, 145, and 171.

At 2 years, MACE was similar between the ZES and PES groups (9.8% vs. 10.0%, p = 0.93). However, the incidence of MI (2% vs. 4.1%, p = 0.023), mainly non–Q-wave MI (1.6% vs. 3.5%, p = 0.022), was significantly lower in the ZES arm. Target vessel failure was similar between the two arms (11.1% vs. 13.1%, p = 0.23). The disturbing trend of increased stent thrombosis with ZES up to 1 year was not evident at 2 years of follow-up: Only one other stent thrombosis occurred in the ZES arm, compared with six in the PES arm, with an overall stent thrombosis rate of 1.9% vs. 1.6% at 2 years (p = 0.84).

At 3 years, preliminary unpublished data showed that the overall incidence of cardiac death and MI was significantly lower in the ZES arm compared with PES (3.7% vs. 7.1%, hazard ratio 0.52, 95% confidence interval 0.32-0.82, p = 0.005), primarily driven by a significant reduction in MI (2.2% vs. 4.9%, p = 0.007). All-cause mortality was similar (4.0% vs. 4.5%, p = 0.70). The primary endpoint of target vessel failure trended towards being lower in the ZES arm (12.4% vs. 16.1%, p = 0.052). The incidence of very late stent thrombosis (360-1,080 days) was significantly lower in the ZES arm (0.1% vs. 1.5%, p = 0.006). The rates of target lesion revascularization (6.5% vs. 6.0%) and MACE (11.4% vs. 13.8%) were similar between the two arms at the end of 3 years.

Interpretation:

Among patients undergoing PCI for a single de novo lesion in a native coronary artery, use of a ZES was noninferior to a PES for the primary endpoint of target vessel failure at 9 months.

The ZES has previously been evaluated in comparison to the sirolimus-eluting stent in the ENDEAVOR III trial, which showed significantly greater late lumen loss with the ZES on angiographic follow-up. Similar results were observed in the present study, which showed greater late lumen loss with the ZES when compared with the PES. The difference in late lumen loss in the angiographic substudy did not translate into a difference in clinical events.

There was no difference in target vessel failure or MACE between the two stents over 2 years of follow-up. The initial trend toward an increase in stent thrombosis noted with the ZES at 1 year was not noted at 2 years, resulting in a similar incidence of stent thrombosis between the two arms at 2 years.

Further, the 3-year results suggest that ZES may actually be superior to PES in reducing MI and very late stent thrombosis, with no difference in death or target lesion revascularization. Final publication of these results is awaited.

References:

Leon MB, Mauri L, Popma JJ, et al., on behalf of the ENDEAVOR IV Investigators. A Randomized Comparison of the Endeavor Zotarolimus-Eluting Stent Versus the TAXUS Paclitaxel-Eluting Stent in De Novo Native Coronary Lesions: 12-Month Outcomes From the ENDEAVOR IV Trial. J Am Coll Cardiol 2009;55:543-54.

Leon MB, Kandzari DE, Eisenstein EL, et al. Late Safety, Efficacy, and Cost-Effectiveness of a Zotarolimus-Eluting Stent Compared With a Paclitaxel- Eluting Stent in Patients With De Novo Coronary Lesions: 2-Year Follow-Up From the ENDEAVOR IV Trial (Randomized, Controlled Trial of the Medtronic Endeavor Drug [ABT-578] Eluting Coronary Stent System Versus the Taxus Paclitaxel-Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions). JACC Cardiovasc Interv 2009;2:1208-18.

Three-year data presented by Dr. Martin B. Leon at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2009), San Francisco, CA, September 21, 2009.

Also presented by Dr. Martin B. Leon, at TCT 2007 and 2008, Washington, DC.

Keywords: Paclitaxel, Myocardial Infarction, Coronary Restenosis, Coronary Stenosis, Thrombosis, Constriction, Pathologic, Coronary Vessels, Sirolimus, Stents, Percutaneous Coronary Intervention


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