SAN FRANCISCO – The first trial in humans of a bioabsorbable polymer-coated everolimus-eluting coronary stent found it was noninferior to a durable-polymer everolimus-eluting stent in a multicenter randomized, single-blind study.
The study randomized 291 patients at 29 sites to receive the permanent-polymer everolimus-eluting Promus Element stent or one of two versions of the bioabsorbable everolimus-eluting Synergy stent. One group received a Synergy stent with an everolimus dose and release profile similar to that of the Promus Element stent; the other received a Synergy stent with half the dose of everolimus.
Patients were treated for new coronary lesions measuring no more than 28 mm in length with a coronary artery reference vessel diameter of 2.25-3.5 mm.
At 6 months of follow-up, average in-stent late loss (the amount of lesion tissue regrowth) was 0.15 mm in the Promus Element group, 0.10 in the full-dose Synergy group, and 0.13 in the half-dose Synergy group. The differences between the Promus Element group and either of the biodegradable stent groups were not significant, proving noninferiority of the Synergy stents, Ian T. Meredith, Ph.D., and his associates reported Nov. 11 at Transcatheter Cardiovascular Therapeutics 2011, sponsored by the Cardiovascular Research Foundation.
Dr. Ian Meredith
At 30 days and 6 months of follow-up, rates of target lesion failure did not differ significantly in the 98 patients in the Promus Element group, compared with either the 94 patients in the full-dose Synergy group or the 99 patients in the half-dose Synergy group. These findings suggest that the bioabsorbable Synergy stents are as safe as durable-polymer stents, said Dr. Meredith, director of Monash Heart Medical Centre and professor of medicine at Monash University, Melbourne.
Target lesion failure was defined as cardiac death or MI related to the target vessel or target lesion revascularization.
At 3 months, target lesion failure occurred in none of the patients who received the Promus Element stent, 1% of the full-dose Synergy group, and 3% of the half-dose Synergy group. At 6 months, the rates were 3%, 2%, and 4%, respectively. The differences in rates between the Promus Element group and either of the Synergy groups were not statistically significant at either time point.
"What we’ve tested in this trial is whether you can go from delivering the same dose of drug on a conformable durable polymer of a certain load, reduce that polymer load to a tiny fraction of what you have with a durable polymer, release the same drug with the same kinetic profile and the same load, and achieve the same results. The answer is that you can," he said at a press briefing. "In fact, you can go to even half the drug dose on that polymer again and still achieve the same results at 6 months."
The caveats are that these were relatively straightforward lesions in noncomplex patients with only 6 months follow-up so far. "But it certainly proves the concept," he added.
The study was not powered to detect differences in clinical events.
Commenting on the study at a press briefing, Dr. Ron Waksman, director of experimental angioplasty at the Washington Hospital Center, expressed some concern about fairly large standard deviations around the mean estimates of late loss, but said he is "always excited" by any bioavailable polymer technology that shows noninferiority to durable stents.
Dr. Roxana Mehran
Dr. Roxana Mehran, professor of medicine and director of interventional cardiovascular research at Mount Sinai School of Medicine, N.Y., said it will be challenging for the investigators to design a clinical trial that might show "something that’s exciting and different. That will be a challenge, because event rates are low," she said.
Dr. Meredith noted that the Prodigy stent uses a thinner bioabsorbable polymer coating – 3-5 mcm thick – compared with the BioMatrix Flex biodegradable polymer biolimus-eluting stent. Earlier at this meeting, other investigators reported 4-year results with the BioMatrix stent, showing noninferiority to durable drug-eluting stents and possibly improved clinical outcomes.
Patients in the current study had a mean age of 63 years, 73% were male, and 19% were being treated for diabetes.
More research on the Synergy stents are needed to evaluate clinical event rates and to explore the possibility of reducing the need for dual-antiplatelet therapy in patients receiving bioabsorbable stents, he said.
The Synergy stent is a thin-strut, platinum chromium stent platform loaded with everolimus delivered by an ultrathin bioabsorbable polymer applied to the abluminal surface of the stent. Durable polymers on drug-eluting stents have been associated with chronic inflammation and impaired healing. The polymer on the Synergy stent is reabsorbed by 4 months after implantation.