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A novel dual-technology stent aimed at preventing restenosis while promoting healing showed angiographic noninferiority compared with a first-generation drug-eluting stent, according to results of a small, first-in-man study published online March 20, 2013, ahead of print in JACC: Cardiovascular Interventions.

The angiographic data were originally presented at the Transcatheter Cardiovascular Therapeutics (TCT) scientific symposium in San Francisco, CA, in November 2011, while 12-month clinical data were presented at EuroPCR in Paris, France, in May 2012.

For the international study, investigators led by Michael Haude, MD, PhD, of Lukas Hospital (Neuss, Germany), randomized 183 patients with de novo coronary artery stenosis in a 2:1 ratio to the sirolimus-eluting dual-therapy Combo stent (OrbusNeich, Ft. Lauderdale, FL; n = 124) or the paclitaxel-eluting Taxus Liberté stent (PES; Boston Scientific, Natick, MA; n = 59).

The Best of Both Worlds

The Combo stent combines sirolimus elution from an abluminal biodegradable polymer matrix with a thin coating of CD34 antibodies to capture circulating endothelial progenitor cells. The polymer technology aims to improve stent efficacy by limiting neointimal proliferation and chronic inflammation, while the cell capture strategy is designed to accelerate vessel healing and stent strut endothelialization to minimize late stent thrombosis.

Rates of procedural success were similar between the Combo and PES groups (96.8% and 98.3%; P = 1.00). At 9-month angiographic follow-up, the Combo stent proved noninferior to PES for in-stent late lumen loss, the primary endpoint. Other angiographic parameters, including in-segment late lumen loss, in-stent binary restenosis, and in-stent minimum lumen diameter, were also similar, with a trend toward lower in-segment late lumen loss with the Combo stent (table 1).

Table 1. Nine-Month Angiographic Results

^a For noninferiority.

Follow-up IVUS at 9 months, performed in a subgroup of 52 patients, showed numerically lower neointimal hyperplasia volume in the Combo group compared with the PES group (21.5 ± 21.7 mm³ vs. 25.9 ± 18.7 mm³; P = 0.4955). In addition, IVUS-based virtual histology showed less necrotic core area at maximum site on neointimal hyperplasia (0.25 mm² vs. 0.46 mm²; P = 0.04) and a less confluent necrotic core (10% vs. 80%; P = 0.02).

Meanwhile, interim results from the EGO-COMBO substudy, in which 60 patients at a single center were analyzed with OCT, showed 70% strut coverage at less than 50 days, and nearly 100% coverage at about 140 days (presented by Lee ST at TCT 2011).

In REMEDEE, 12-months event rates were low and similar for both groups. Of 2 reported deaths (both in the Combo group), 1 was adjudicated as a cardiac death. In particular, there were no cases of Academic Research Consortium-defined definite or probable stent thrombosis (table 2).

Table 2. Clinical Events at 12 Months

^a MACE defined as death, MI, emergent CABG, or TLR.

The Combo stent incorporates features that could make it an ideal DES, at least in theory, David E. Kandzari, MD, of the Piedmont Heart Institute (Atlanta, GA), told TCTMD in a telephone interview. “But for me, this study is limited in the answers it provides” about whether that promise will be fulfilled, he said.

Late Loss an Outdated Endpoint?

“While the angiographic outcomes are noninferior to the PES, a paclitaxel-eluting stent today is not the standard for comparison,” he observed. “Also, the emphasis on late lumen loss has waned in the past several years, in part because today’s DES have such low angiographic late loss that clinical efficacy among them is similar.” Furthermore, he noted, the late loss value for the Combo stent is one of the highest observed for a sirolimus-eluting stent.

Dr. Kandzari said the trial is also disappointing in that it does not address issues that could have supported the experimental stent’s concept and helped differentiate it from other, new-generation DES.

“If you’re going to evaluate a new DES that is intended to improve healing and perhaps safety, it should be tested in a trial that doesn’t just conform to the historical model of late loss and TLR,” he asserted.  For example, the study should have assessed the patterns of healing with serial imaging and tested vasomotor function. It also missed an opportunity to inform clinical dilemmas by testing abbreviated dual antiplatelet therapy, he added.

Stent Covered with ‘Friendlier’ Tissue

But in a telephone interview with TCTMD, study coauthor Roxana Mehran, MD, of Mount Sinai Medical Center (New York, NY), pointed to the OCT substudy as yielding the most interesting finding. “It shows significant differences in the composition and distribution of tissue covering the Combo stent compared with the first-generation DES,” she noted. “The tissue has less necrotic core and is more uniform—it’s just a lot friendlier [in terms of avoiding events]”

Dr. Mehran acknowledged that the clinical results in this small angiographic study are not meaningful. However, she noted, “there were no [clinical] issues” with the Combo stent, and TLR rates were marginally lower than for the PES.

Dr. Mehran predicted CE mark approval for the Combo stent, followed by a prospective registry and then a pivotal randomized trial with a newer-generation DES as the comparator. “I look forward to prospective studies to prove the Combo concept,” she concluded.

Note: Dr. Mehran and several other coauthors are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.

 

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Source:
Haude M, Lee SWL, Worthley SG, et al. The REMEDEE trial: A randomized comparison of a combination sirolimus-eluting endothelial progenitor cell capture stent with a paclitaxel-eluting stent. J Am Coll Cardiol Intv. 2013;Epub ahead of print.

 

 

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