May 16, 2008 (Barcelona, Spain) - Physicians at this year's EuroPCR meeting had the chance to glimpse some of the first randomized clinical data on so-called "active" stents that promote vessel healing while reducing the risk of antiproliferative reactions, without carrying polymers or drugs that have been blamed for an increased risk of stent thrombosis.
Whether such stents end up competing directly with blockbuster drug-eluting stents (DES) or end up as niche products in people who cannot take dual antiplatelet therapy remains to be seen, experts say.
The Genous stent is an antibody-coated bare-metal stent designed to capture a patient's own endothelial progenitor cells (EPCs) to accelerate the natural healing process after stent placement and to modulate smooth-muscle-cell growth. Stent developers believe the stent would be particularly attractive to patients who cannot take extended dual antiplatelet therapy or who may be at particularly high risk for stent thrombosis.
Investigators for the e-Healing multicenter first-in-human registry of the Genous stent (OrbusNeich) and for the TRIAS-HR randomized pilot study comparing the Genous stent with the Taxus stent presented new data here at the meeting. The e-Healing registry, led by Dr Sigmund Silber (Dr Müller Hospital, Munich, Germany) and Dr Robbert de Winter (Academic Medical Center, Amsterdam, the Netherlands) had, as of late March 2008, enrolled almost 5000 patients at 144 sites. In an interim analysis of 1640 patients who have completed 12-month follow-up, investigators report that rates of cardiac death, MI, and target lesion revascularization (TLR) are low and comparable with rates seen in the early Taxus registry studies. Importantly, a low rate of stent thrombosis was seen despite patients taking just one month of dual antiplatelet therapy.
e-Healing Registry: 12-Month Results
|End point||12 mo (%)|
de Winter also presented 12-month results from the randomized TRIAS-HR pilot study, a single-center randomized controlled trial comparing the Genous with the Taxus stent in high-risk patients (long lesions, small vessels, chronic total occlusions, or any lesion in a diabetic patient). As he explained to heartwire , TRIAS-HR had been designed to enroll a larger patient population but was closed after one year in order to switch to the larger multicenter study.
In all, 98 patients were randomized to the Genous stent, followed by one month of dual antiplatelet therapy, and 95 patients randomized to the Taxus, with at least six months of dual antiplatelet therapy. At 12 months, the rate of MI was numerically higher in Taxus-treated patients (n=5 vs 1) but TLR rates were higher in Genous-treated patients (n=11 vs 8).
In an interview with heartwire , de Winter emphasized that the trial was not powered to detect differences in clinical events, but there are at least early signs that while the Genous may not be as effective at reducing restenosis, it may be associated with less stent thrombosis--the likely cause of the MIs in the Taxus-treated patients. "And of the infarctions in the Taxus-treated patients, four of these were large infarcts, likely due to stent thrombosis," he said.
Whether these trends, in a small trial, will prove important in a larger study group is unknown, he continued.
"It's not something we can determine from this study, because this pilot study was clearly underpowered, but if you look at the risk of repeat revascularization for clinical restenosis in most instances, these are very low-risk procedures," de Winter explained. "And even if you have an incidence of periprocedural MI in the redo procedures, those are small infarcts compared with the generally big infarcts that are associated with stent thrombosis. So I think this trade-off will translate, in the end, into clinical benefit or clinical equality."
The original TRIAS-HR study has now been extended and will be part of the TRIAS-High-Risk (HR) multicenter study with an intended enrollment of 1200 patients comparing the Genous with a market-approved DES (so far the Cypher or the Taxus, although investigators are considering inclusion of the Xience V). A second TRIAS-Low-Risk (LR) study has also been launched, also with a target enrollment of 1200 patients, comparing the Genous with a bare-metal stent in low-risk patients.
The big question is whether the Genous will end up being a niche device, used primarily in patients where an as-yet-unproven, minimally increased risk of revascularization may be a reasonable trade-off for reduced stent thrombosis in higher-risk patients or in patients who cannot take clopidogrel, for a range of reasons. In e-Healing, de Winter noted, one of the top enrolling countries was Malaysia, where patients seem to suffer from a higher rate of gastrointestinal bleeding on dual antiplatelet therapy.
"The niche is probably going to be much larger than just the occasional patient with a clopidogrel allergy," he told heartwire . "But it depends on what comes out of the randomized study. If we are able, in 1200 patients, to repeat the findings we saw in the pilot study, namely a slight increase in TLR but also a much lower risk of stent thrombosis, then we may have a safer stent that is more or less equally effective." If that's the case, he said, "I think this is going to be a competitor with DES, depending on type of lesion and types of patients."
Commenting on the study for heartwire , Dr Roxana Mehran (Columbia University, NY) also underscored the need for the large randomized clinical trial results, but she hinted that the efficacy benchmark set by DES may be tough to match.
"I think this product will be interesting for those patients in whom antiplatelet therapy will be an issue," she said. "More data are absolutely needed to prove the efficacy and safety of this stent."
According to de Winter, over 500 patients have already been enrolled in the TRIAS-HR/LR trial, and investigators expect to complete trial enrollment by the end of the year. The study is designed with one-year target lesion failure as the primary end point, with an angiographic substudy at 13 months.
De Winter disclosed having no personal financial relationship with OrbusNeich but noted that the multicenter trial is funded in part by an unrestricted grant from the company.
Heartwire from Medscape © 2008 Medscape
Cite this: Shelley Wood. First Clinical Data on "Healing" Stents Hint at Reduced Stent Thrombosis, But Also Increased Restenosis - Medscape - May 16, 2008.