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A novel polymer-free, sirolimus-eluting stent shows angiographic superiority to a first-generation paclitaxel-eluting stent at 6 months, according to a study published online January 25, 2012, ahead of print in the Journal of the American College of Cardiology. Although no significant advantage was seen in 1-year clinical outcomes, the authors say this technology nonetheless has the potential to reduce the late stent thrombosis associated with conventional permanent-polymer drug-eluting stents (DES). 

The findings from the prospective, multicenter NEXT trial were originally presented November 11, 2011, at the annual Transcatheter Cardiovascular Therapeutics scientific symposium in San Francisco, CA. 

Investigators led by Didier Carrié, MD, PhD, of Centre Hospitalier Universitaire Rangueil (Toulouse, France), randomized 323 patients with single de novo lesions undergoing PCI to the polymer-free Cre8 stent (n = 162; Carbostent and Implantable Devices; Saluggia, Italy) or Taxus Liberté (n = 163; Boston Scientific; Natick, MA).

The Cre8 device features a thin cobalt-chromium alloy platform with a passive carbon coating designed to promote endothelialization and reduce thrombogenicity. An amphilimus drug formula consisting of sirolimus plus organic acids that enhance bioavailability is loaded into abluminal reservoirs to target drug to the vessel wall.

Baseline clinical presentation and lesion characteristics were similar between the stent groups.

Cre8 More Effective

At 6 months, QCA parameters were analyzable for 276 patients with 316 lesions (160 Cre8, 156 Taxus). Late lumen loss, the primary endpoint, was reduced by 60% in the Cre8 arm compared with the Taxus arm, meeting the criteria for both noninferiority and superiority. In-stent minimal lumen diameter (MLD) and in-stent diameter stenosis were also improved in the Cre8 group, while there was no difference between the devices for in-stent binary restenosis (table 1).

Table 1. Six-Month QCA Outcomes

^a P value for both noninferiority and superiority.

In addition, 6-month IVUS analysis, available in 48 patients (27 Cre8, 21 Taxus), showed Cre8 to be superior for the prespecified endpoints of neointimal hyperplasia volume (11.8 ± 8.2 mm³ vs. 18.7 ± 10.1 mm³; P = 0.009) and volume obstruction (6.7 ± 2.4% vs. 11.3 ± 5.6%; P = 0.001).

At 1 year, no differences were seen in cumulative clinical outcomes, including all-cause death, MI, TLR, MACE (death, MI, and TLR), and Academic Research Consortium-defined definite and probable stent thrombosis (table 2).

Table 2. Clinical Outcomes at 12 Months

 
However, there was a trend toward more cumulative adverse cardiac events in the Taxus arm than the Cre8 arm (7.8% vs. 6.5%), which was maintained in a diabetic subgroup (11.1% vs. 4.5%).

Currently, nonpolymer DES stents are the focus of great interest, observed Stephen G. Ellis, MD, of the Cleveland Clinic (Cleveland, OH), in a telephone interview with TCTMD. “There are a number of them in trials and development because the polymer has been accused of being involved in stent thrombosis, particularly late and very late stent thrombosis,” he noted. “Data from the LEADERS trial make these [devices] look superior to biostable polymer devices, at least if you do a landmark analysis from a year looking at MACE or stent thrombosis.”

The authors also suggest that the distinctive features of the Cre8 stent “may take a role in reducing the need for prolonged dual antiplatelet therapy.”

Is Taxus an Appropriate Comparator?

However, Dr. Ellis said he was perplexed as to why the investigators chose to compare Cre8 to Taxus. The first-generation stent is “hardly a gold standard,” he commented, pointing to a meta-analysis pitting Xience vs. Promus vs. Taxus in which Taxus came out third best.

On the other hand, Ajay J. Kirtane, MD, SM, of Columbia University Medical Center (New York, NY), suggested in a telephone interview with TCTMD that Taxus was probably chosen as a comparator simply because it is easier to gain study power using the mainstream DES. Moreover, Taxus Liberté is a relatively effective stent, he added.

Dr. Ellis called the late loss results [for Cre8] “not outstanding” but probably good enough to merit a larger trial. He added that there are far too few patients in the current study to evaluate the new stent’s safety.

Dr. Kirtane was more specific. “What I would like to see now is a head-to-head larger study that randomizes Cre8 against Xience or Resolute, and [is powered for] clinical outcomes,” he said.

Overall, the hypothesis that eliminating the polymer will minimize adverse effects is very attractive, Dr. Kirtane said, and “these data show that that could be a good strategy. In fact, if these results hold up in a larger study, [the polymer-free stent design] may be the next wave of innovation in DES.”

One challenge, however, is that because of the effectiveness of new-generation DES, “it gets harder and harder to show incremental benefits” with a new technology, Dr. Kirtane noted.

“That having been said, we’re all in favor of anything that makes PCI safer and more efficacious for our patients,” he concluded.

Study Details

Predilation was mandatory. Available stent sizes were 3.0 mm and 3.5 mm, while stent lengths ranged from 12 mm to 25 mm.

Periprocedural anticoagulation was heparin or bivalirudin with administration of glycoprotein IIb/IIIa inhibitors according to local practice. Postprocedure dual antiplatelet therapy was mandated for at least 6 months, with indefinite continuation of aspirin.

Related Stories:

• ISAR-TEST 5 Published: Polymer-Free Dual DES Noninferior to Resolute
• ISAR-TEST-2 Published: Polymer-Free Dual-DES Shows Sustained Efficacy