Small Trial for Innovative 'Healing' Stent Contradicts Findings from Larger Studies

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March 29, 2009 -- Cardiologists anticipating positive results from a small head-to-head study comparing the novel Genous "pro-healing" stent to a third generation bare metal chromium-cobalt stent were disappointed yesterday by less than favorable data from the 100-patient GENIUS-STEMI study.

The presentation was made during the i2 Summit of the American College of Cardiology’s 58th annual scientific session by Dr. Pavel Cervinka, head of cardiology at Masaryk Hospital and University of J.E. Purkyne, Ústí nad Labem, Czech Republic.

Genous ECP "Healing" stent

The study population was restricted to heart attack patients presenting with ST-Elevated Myocardial Infarction (STEMI) who were then randomized: 50 patients got a bare-metal stent; 50 received the novel Genous endothelial progenitor cell (EPC) device. The results were not favorable for the Genous stent: the rate of Major Adverse Coronary Events (death, heart attack, revascularization) was 24% for the Genous vs. 10% for the bare metal stent. Target Lesion Revascularization (TLR) was 14% vs. 4%. Not only were these rates very high, but they were far different from data that has been presented in the initial clinical trials for the Genous, as well as a very large 5,000-patient observational study, called the e-Healing Registry.

Co-investigator of the e-Healing study, Dr. Sigmund Silber, MD, FACC, FESC, chief of cardiology at Müller Hospital Munich in Munich, previously had presented the one-year follow-up for the first 1,640 patients at November's American Heart Association meeting. Although a registry differs from a randomized clinical trial, it often more accurately mirrors the real-world use of a device. In fact, outcomes from the e-Healing Registry were better by factors of 3: MACE was 9.3%, TLR was 5.4% and total stent thrombosis was only 1%, giving credence to the chief characteristic of the Genous stent -- safety and efficacy without the need for long-term dual antiplatelet therapy.

Angioplasty.Org asked Dr. Silber his reactions on the negative findings for GENIUS-STEMI and he commented:

"This was a small study, underpowered for clinical events. This shows again that we need larger randomized trials before drawing any conclusions. A new device should be evaluated first in a small registry study (ca. 100 patients), then, if it goes in the desired direction, a large randomized trial with a primary clinical endpoint should follow, preferably an all comers randomized trial. This stepwise procedure should be followed by the industry, avoiding these discussions."

Sigmund Silber, MD

Dr. Silber will be presenting additional data from the e-Healing registry at next month's Annual Meeting of the German Society of Cardiology in Mannheim.

The Genous EPC stent is uniquely conceived. It is not a drug-eluting stent, but rather is coated with an antibody that binds endothelial progenitor cells (EPC) circulating in the blood. These cells then promote healing and cover the metal stent with endothelium. Drug-eluting stents work almost the exact opposite way, by eluting a drug that suppresses cell growth, to keep the stent from reblocking. However, that same characteristic causes drug-eluting stents to delay healing and prolong the period when platelets can aggregate around the stent struts, causing blood clots or thrombosis, often resulting in a heart attack.

Although late and very late stent thrombosis in drug-eluting stents is very small in percentage, the results can be catastrophic. Moreover, in order to prevent stent thrombosis, patients must stay on aspirin and clopidogrel (Plavix) for 6-12 months or longer, which can result in bleeding complications and which complicates subsequent surgical procedures for the patient. With the Genous stent, only 30 days of antiplatelet therapy is necessary -- which is why the very low total stent thrombosis rate of 1% at 12 months is striking. Researchers believe that, while the Genous stent may not suppress restenosis as forcefully as a drug-eluting stent, the benefits are many, especially in patients unable to comply with a strict antiplatelet regimen.

Jeffrey J. Popma, MD

Commenting officially on the GENIUS-STEMI report at the ACC, Dr. Jeffrey Popma of St. Elizabeth's Medical Center in Boston was concerned over the safety issues and opined that researchers might need to go back to the drawing board. He stated:

"Maybe with this particular technology, rather than larger randomized, controlled trials, we should go back to some of the basics of proof of concept.... Are endothelial progenitor cells truly captured using this design in patients undergoing PCI, particularly for STEMI, and if they're captured, are they functional? To date with this design, we have not seen any evidence that it reduces clotting or the renarrowing of arteries. Maybe we should go back and look at some of the fundamental concepts of this technology."

It may be that in the setting of STEMI, the endothelial progenitor cells work differently -- perhaps due to the more thrombogenic environment. However, even Dr. Cervinka cautioned against over-interpreting the results from this small, single-center study. Only 50 patients received a Genous stent, so the outcomes from a single patient could change the total results by two percentage points.

Reported by Burt Cohen, March 29, 2009