ORLANDO, FL—An innovative stent technology suffered a blow when 6-month results revealed that heart attack patients treated with the investigational device had higher rates of major adverse cardiac events (MACE) and target lesion revascularization (TLR) than similar patients treated with bare-metal stents, according to late breaking trial results presented Saturday, March 28, 2009 at the American College of Cardiology Scientific Sessions/i2 Summit.

The Genous stent (OrbusNeich, Hong Kong, China) is coated with antibodies that bind circulating endothelial progenitor cells to promote normal arterial healing and endothelialization after stent implantation. The idea is to reduce restenosis and avoid the slightly raised risk of late thrombosis that can accompany drug-eluting stents.

In the GENIUS-STEMI (GENous stent versus chromIUm-cobalt Stent for treatment of ST-Elevation Myocardial Infarction) trial, researchers led by Pavel Cervinka, MD, PhD, of Masaryk Hospital (Usti nad Labem, Czech Republic) prospectively randomized 100 consecutive STEMI patients at their institution to primary PCI with the Genous stent or a bare-metal chromium-cobalt stent between January 2007 and December 2007. Both groups were administered dual antiplatelet therapy for 30 days.

At 6 months, the rate of MACE (CV death, MI, and TLR) was significantly increased in patients receiving the Genous stent, driven mainly by an increase in TLR. A higher rate of ARC-defined late stent thrombosis resulting in 3 cases of STEMI also occurred with the Genous stent, although the increase was not statistically significant (table 1).

Table 1. Six-Month Clinical Outcomes

At 6-month angiographic follow-up, patients receiving the Genous stent had more late lumen loss (0.89 ± 0.59 mm vs. 0.79 ± 0.47 mm) and restenosis (20% vs. 13%), but the differences were not statistically significant. A higher, non-significant increase in mean in-stent neointimal hyperplasia was also found with the Genous stent (49.7 ± 48 mm³ vs. 40.0 ± 22.8 mm³).

“The rate of 6-month MACE in the [Genous] stent group was significantly higher when compared to cobalt-chromium stents,” Dr. Cervinka said. “Furthermore, the finding of 6% late stent thrombosis in the [Genous] stent group is worrisome.”

Larger Trials Debated

Nevertheless, Dr. Cervinka urged for further study before abandoning the Genous stent technology.

“I would like to point out before generalizing our results that the trial was a small, single-center study,” he said. “The trial was definitely underpowered for clinical endpoints, and furthermore, there was no QCA or IVUS core lab analysis. Larger, randomized trials are mandatory to finally address these [safety] issues.”

However, session co-moderator Spencer B. King III, MD, of Saint Joseph’s Heart and Vascular Institute (Atlanta, GA) was not sure that would be an easy sell. “We’d all love to learn whether this technology is going to be helpful, but it would be a little hard for my [institutional review board] to go for that with the current evidence,” he said. “How do you go from these kind of data to a larger, randomized trial?”

Back to the Drawing Board

According to Jeffrey J. Popma, MD, of Caritas Christi Health Care (Boston, MA), trials investigating the Genous stent need to go back to the proof-of-concept stage.

“First of all, are the endothelial progenitor cells truly captured using this design in patients undergoing PCI for STEMI? And if they’re captured, are they functional?” he asked. “Some early studies with endothelial activity may be useful.”

Dr. Popma added that “to date with this design, we have not seen any evidence that endothelial progenitor cell capture reduces the degree of intimal hyperplasia and lowers restenosis. There was a concept that more rapid re-endothelialization may lower the degree of intimal hyperplasia. We just haven’t seen that with this technology.”

In terms of explaining the current study results, “I keep coming back to the thrombotic burden in patients with STEMI,” Dr. Popma said. “Maybe there’s too much thrombus that’s left behind for this technology to really be effective in preventing stent thrombosis.”

Either way, “although [Dr. Cervinka’s] conclusion was that maybe the study is too small to demonstrate clinical benefit, I think it’s too large to dismiss the stent thromboses that occurred following the placement of the stent,” Dr. Popma said. “Maybe we should go back and look at some of the fundamental concepts with this important technology.”

Source:

Cervinka P. A Randomized Comparison of Genous Stent Versus Chromium-Cobalt Stent for Treatment of ST-Elevation Myocardial Infarction. A 6-Month Clinical, Angiographic and IVUS Follow-Up. GENIUS-STEMI Trial. Presented at: American College of Cardiology Scientific Sessions/i2 Summit. Saturday, March 28, 2009, Orlando, FL.

Disclosures:

• Drs. Cervinka and Popma declared no relevant conflicts of interest.