TRIAS HR Published: Genous Stent Doubles Target Lesion Failure

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A novel stent—designed to capture circulating endothelial progenitor cells and thus promote healing—has failed to reduce target lesion failure (TLF) at 1 year compared with numerous conventional drug-eluting stents (DES), according to a paper published in the August 2011 issue of JACC: Cardiovascular Interventions. The results were so disappointing, in fact, that the study stopped enrolling patients in early 2009 after an interim analysis.

Data from the TRIAS HR (TRI-stent Adjudication Study—High Risk of restenosis) trial were previously presented in September 2010 at the annual Transcatheter Cardiovascular Therapeutics symposium in Washington, DC.

When initiated by Robbert J. de Winter, MD, PhD, of Academic Medical Center (Amsterdam, The Netherlands), and colleagues, TRIAS-HR planned to enroll 1,300 patients with stable CAD and high risk of restenosis. But the multicenter trial was stopped early after enrolling only 622 patients. Subjects were randomly assigned to receive a Genous bioengineered R stent (n = 304; Orbus-Neich Medical Technologies, Fort Lauderdale, FL) or 1 of 4 DES (n = 318) based on investigator preference:

• Taxus paclitaxel-eluting stents (Boston Scientific, Natick, MA)
• Cypher sirolimus-eluting stents (Cordis Corporation, Miami, FL)
• Xience V everolimus-eluting stents (Abbott Vascular, Abbott Park, IL)
• Endeavor zotarolimus-eluting stents (Medtronic, Minneapolis, MN)

Follow-up will continue through 5 years among patients already enrolled in the trial.

Baseline clinical and angiographic characteristics were similar between the Genous and DES groups. More than 70% of patients were male, and almost half had diabetes. In addition, 70% of treated lesions were type B2/C.

Difference Largely Due to TLR

On an interim review of half of the planned enrollment, 1-year follow-up showed that the primary endpoint of TLF (cardiac death, target vessel MI, and clinically driven TLR) was elevated in Genous patients, mainly driven by increased TLR. Stent thrombosis rates, meanwhile, were nearly three times higher with the newer device (table 1).

Table 1. One-Year Clinical Outcomes

^a P for noninferiority = 0.98.

Dr. de Winter and colleagues point out that the trial design recommended dual antiplatelet therapy for at least 1 month in Genous patients and 6 months in DES patients. Because of this, there was an approximately 20% absolute difference in dual antiplatelet therapy use between the 2 groups by 1 year.

Disappointing Results for Newer Stent

In an e-mail communication, Dr. de Winter told TCTMD that, after having begun TRIAS HR backed by encouraging results from 2 previous studies, the trial’s findings were a letdown.

Sorin J. Brener, MD, of Weill Cornell Medical College (New York, NY), agreed. “It is obviously disappointing that the trial didn’t show what investigators were planning,” he said in a telephone interview with TCTMD. “They probably did not quite get the right kind of anti-CD34+ antibodies that were sufficient to attract progenitor cells from the blood stream.”

Dr. Brener added, however, that he did not think researchers should abandon this technology but should instead perfect it. “We need a better way to imbed the antibodies so that they are sufficiently exposed to the blood stream to attract those cells,” he advised.

In addition, Dr. de Winter pointed out that the trial was not only testing noninferiority at 1-year, but also superiority at 5 years. With continued follow-up in patients already enrolled, he expects to see an accumulation of late and very late stent thrombosis and possibly late TLR with DES.

Can’t Compete with Second-Generation DES

Although the 5-year results remain to be seen, it is important to remember that TRIAS HR mainly compares Genous with first-generation DES, said David E. Kandzari, MD, of the Piedmont Heart Institute (Atlanta, GA).

“The DES arm of the study was mostly paclitaxel-eluting stents and zotarolimus-eluting stents. There were very few second-generation stents,” he told TCTMD in a telephone interview. “Recognizing that TLR largely drove the difference in the composite endpoints between the [treatment groups] in the trial, we would only expect now that with the commonly used second-generation stents that the difference between [Genous] and DES would be even greater.”

According to Dr. Kandzari, these data are enough to make a final conclusion about the cell-capture technology.

“Theoretically, the mechanism for this stent technology is attractive—capturing endothelial progenitor cells to promote more rapid and hopefully complete healing with a stent—but much remains unknown, and to date, as demonstrated by these data and previous studies, it remains clinically unproven,” Dr. Kandzari said.

 

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Source:
Klomp M, Beijk MA, Varma C, et al. 1-year outcome of TRIAS HR (TRI-stent Adjudication Study—High Risk of restenosis): A multicenter, randomized trial comparing Genous endothelial progenitor cell capturing stents with drug-eluting stents. J Am Coll Cardiol Intv. 2011;4:896-904.

 

 

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