ACC 2009: "Healing" Stent Suffers Compared With Bare-Metal Stent in Tiny STEMI Trial

from <a href="http://theheart.org/" target="_blank">Heart<i>wire</i></a> &#151; a professional news service of WebMD

March 28, 2009

March 28, 2009 (Orlando, Florida) — The innovative Genous stent (OrbusNeich), with its clever mechanism for promoting endothelial-cell growth on its blood-exposed surface, which has demonstrated promise against stent thrombosis and CV events in previous observational studies, failed to honor that promise in a small randomized feasibility study in patients with ST-segment elevation MI (STEMI) [1].

In the 100-patient feasibility and safety study of the device, patients who received the Genous stent turned in significantly higher rates of major adverse cardiac events (MACE) and target lesion revascularization (TLR) over six months compared with those getting chromium-cobalt stents, and it was associated with the study's only three instances of stent thrombosis.

The results of the Randomized Comparison of Genous Stent vs Chromium-Cobalt Stent for Treatment of ST-Elevation Myocardial Infarction (GENIUS-STEMI) trial were presented by Dr Pavel Červinka (University of JE Purkyne, Ústi nad Labem, Czech Republic) here today during the i2 Summit at the American College of Cardiology 2009 Scientific Sessions.

Červinka said the stent is "feasible and safe acutely and at 30 days" and called the stent-thrombosis issue "worrisome" but held that GENIUS-STEMI isn't the final word due to its small size, especially given the stent's earlier favorable performances (as reported by heartwire ). He called for larger randomized studies of the device. Still, he said, "It's fair to say that the chromium-cobalt stent did very well in this trial."

The stainless-steel Genous is coated with "immobilized" murine monoclonal antibodies with affinity for surface antigens on native circulating endothelial progenitor cells (EPCs), which are naturally attracted to sites of vascular injury. It's designed so that the antibodies can "capture" EPCs from the circulation so they can blanket the stent's blood-exposed surface. As confirmed in porcine histopathologic studies, Červinka told heartwire , the EPCs indeed cover the stent struts and develop into endothelial cells.

Hopes have been that the Genous would overcome an important limitation of drug-eluting stents, impairment of long-term endothelialization and consequent need for prolonged dual antiplatelet therapy to prevent late stent thrombosis. Importantly, patients in both GENIUS-STEMI groups and in some earlier Genous studies were on dual antiplatelet therapy for only 30 days.

Assigned to formally comment on the study after Červinka's presentation, Dr Jeffrey J Popma (St Elizabeth Medical Center and Harvard Medical School, Boston, MA) observed that the study was small but strengthened by "meticulous attention to details, standard clinical, angiographic, and [intravascular ultrasound] IVUS definitions, and concordance of anatomic and clinical end point."

So, he said, "the results are quite believable. And although the conclusion was that this study was just too small to demonstrate clinical benefit, I think it's too large to dismiss the stent thrombosis that occurred following placement of the Genous stent."

The 100 STEMI patients were evenly randomized to primary PCI with either the Genous or a cobalt-chromium bare-metal stent; glycoprotein IIb/IIIa receptor inhibitors and thrombus aspiration were included at the discretion of physicians. The groups had been clinically and angiographically similar at baseline.

Rates of MACE (conventionally defined as MI, CV death, or clinically driven TLR) and of cardiovascular events were few, with no significant differences between the groups. At six months, however, rates for both MACE and TLR on its own were significantly higher among the Genous recipients.

Six-Month Clinical End Point in GENIUS-STEMI

End point Genous stent, n=50 (%) Chromium-cobalt stent, n=50 (%) p
MACE 24 10 0.03
MI 6 2 NS
Cardiovascular death 4 4 NS
Target-lesion revascularization 14 4 0.04

 

No significant differences were seen in angiographic or IVUS measures of recurrence, although there was a nonsignificant suggestion of an increase in neointimal hyperplasia volume by IVUS in the Genous group (49.7 mm3 vs 40.0 mm3).

All three cases of stent thrombosis among Genous recipients were classified as late-occurring (31 to 360 days), definite thromboses according to the widely adopted Academic Research Consortium (ARC) criteria. None were fatal, Červinka said.

Popma seemed to feel that the Genous stent turned a decisive corner in the GENIUS-STEMI trial. "Maybe with this particular technology, rather than [have] larger randomized, controlled trials, we should go back to some of the basics of proof of concept. First of all, are endothelial progenitor cells truly captured using this design in patients undergoing PCI, particular for STEMI, and if they're captured, are they functional? To date with this design, we have not seen any evidence that endothelial-cell capture reduces the degree of neointimal hyperplasia or lowers [the risk of] restenosis, we just haven't seen that with this technology."

And, he said, "I think we have to show that these endothelial cells generated within the stent are truly functional in order to suspect that there's a link between better healing and lower stent-thrombosis rates. So, I think it's a very important trial, but maybe as a result of it, we should go back and look at some fundamental concepts with this important technology."

Červinka acknowledged to heartwire that, with the Genous, "there have been no histopathologic studies in humans. But we believe it works because we've seen it in porcine arteries." He also acknowledged that the GENIUS-STEMI clinical results suggest otherwise. "But this was the only Genous study showing that result."

Červinka had no disclosures. Popma disclosed receiving research grants from Cordis, Boston Scientific, Medtronic, Abbott-Guidant, Biosensors, eV3, LabCoat; being on the medical advisory board of Cordis, Boston Scientific, and Medtronic; and being on the speaker's bureau for Sanofi, Bristol-Myers Squibb, Boston Scientific, and Pfizer.

 

  1. Červinka P. A randomized comparison of Genous stent vs chromium-cobalt stent for treatment of ST-Elevation myocardial infarction. A 6-month clinical, angiographic and IVUS follow-up. GENIUS-STEMI trial. American College of Cardiology 2009 Scientific Sessions and i2 Summit; March 28, 2009; Orlando, FL. Late-breaking clinical trials 1.

 

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