ETHOS I: No Incremental Benefit with Estradiol-eluting Stents
Lower doses of estradiol will be used in ETHOS II and III, which may show more benefit.
Initial data from ETHOS I, a randomized, controlled trial of estradiol-eluting stents, found no evidence of benefit with the stents compared with bare-metal stents.
The use of Ethos stents (X-Cell Medical, Inc. and SurModics, Inc.) in both moderate- and fast-release formulations did not result in any significant advantage when quantitative coronary angiography and intravascular ultrasound (IVUS) assessments were conducted during follow-up at six months, according to a presentation by Alexandre Abizaid, MD, PhD, of Instituto Dante Pazzanese de Cardiologia in Brazil.
Comparable results
At six-month follow-up, the overall rate of major adverse cardiac events was 18.8% with moderate-release stents, 10.3% with the fast-release stents and 9.4% with the bare- metal stents. There was one death in the moderate-release stent group, and none in the other two treatment arms. No cases of stent thrombosis were observed in any patient group.
Quantitative coronary angiography data also reported similar findings in-stent and in-lesion for the three arms (Figure).
IVUS measurements taken in the same follow-up period indicated no statistically significant differences among the three arms with respect to neointimal hyperplasia volume, volumetric plaque burden and in-stent volume obstruction.
No significant safety concerns were associated with the use of estradiol-eluting stents.
Lower-dose efficacy
Abizaid noted that because preclinical data suggest that using less estradiol may be more effective at enhancing endothelial progenitor cell growth, more treatment benefit may be expected in the ETHOS II and III trials, in which estradiol will be administered at lower doses. Additionally, both trials will use less polymer load.
“If lower dose and lower polymer will indeed be of use, we should really be enthusiastic about seeing the results of ETHOS III,” Abizaid said. “In future trials, a combination of estradiol and an antiproliferative agent may also provide an enhanced safety profile, while maintaining adequate efficacy at low doses.”
Less polymer
Michael J. B. Kutryk, MD, PhD, of the University of Toronto, echoed Abizaid’s comments during the critical commentary session that followed the presentation of ETHOS I data.
“There’s certainly a lot of preclinical evidence that estradiol may be a good agent for the prevention of restenosis and for prevention of thrombosis,” he said. “But can these effects overcome the inflammatory effects of polymer? The ETHOS II uses a much lower dose of estradiol and less polymer load, and the ETHOS III trial uses even lower amounts of both.”
Estradiol can be toxic to progenitor endothelial cells, which may account for the disparate results between the animal models and clinical results, and using less polymer is also healthier for the vessel wall, according to Abizaid.
“This is a technology that has great potential, but it just needs to be proven in a clinical model,” he said.
In the ETHOS I trial, bare-metal stents were given to 32 patients, fast-release Ethos stents to 31 patients and moderate-release Ethos stents to 32 patients. All patients underwent two months of treatment with clopidogrel (Plavix, Sanofi-Synthelabo).
Ethos stents are coated with 17 beta-estradiol, which researchers believe inhibits both intimal proliferation in response to balloon injury and adventitial cell migration, as well as accelerates wound healing. It was hypothesized that these various attributes could reduce restenosis in coronary arteries.