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An investigational bioabsorbable-polymer everolimus-eluting stent (EES) performs as well as its permanent-polymer counterpart, according to early data published online February 15, 2012, ahead of print in the Journal of the American College of Cardiology. But, the authors say, larger, longer trials are needed to pin down clinical benefit, including whether the biodegradable technology will allow for abbreviation of dual antiplatelet therapy.

The findings were originally reported in November 2011 at the annual Transcatheter Cardiovascular Therapeutics scientific symposium in San Francisco, CA.

For the first-in-human EVOLVE trial, investigators led by Ian T. Meredith, MBBS, PhD, of Monash Medical Centre Clayton (Melbourne, Australia), randomized 291 patients at 29 international centers to the biodegradable-polymer Synergy EES at full (n = 94) or half-drug dose (n = 99) or the permanent-polymer Promus Element EES (n = 98; all Boston Scientific, Natick, MA).

Same Platform, Different Polymer

While Synergy and Promus Element share the same thin-strut platinum-chromium alloy platform, Synergy delivers everolimus from an ultrathin bioabsorbable poly (DL-lactide-co-glycolide) polymer present only on the abluminal surface. In preclinical testing, strut endothelialization was reportedly achieved within 28 days of implantation and polymer reabsorption completed within 4 months.

Baseline clinical and angiographic characteristics were similar among the 3 groups, except for a larger reference vessel diameter in the Synergy half-dose group compared with the Promus group (2.65 ± 0.40 mm vs. 2.53 ± 0.41 mm; P = 0.04). Implantation was successful in virtually all patients.

At 30 days, the primary clinical endpoint of target lesion failure (TLF; composite of cardiac death, target-vessel MI, or ischemia-driven TLR) and the individual endpoints were similar between Promus Element and both Synergy groups. The same pattern was seen at 6 months (table 1).

Table 1. Clinical Outcomes at 30 Days and 6 Months

In addition, there were no cases of Academic Research Consortium-defined definite or probable stent thrombosis at either time point. All 4 TLF events in the Synergy groups were attributable to non-Q-wave MI.

At 6 months both the Synergy and Synergy half-dose devices proved noninferior to Promus Element for the primary angiographic endpoint of in-stent late loss as assessed by quantitative coronary angiography. In certain other angiographic metrics, such as in-stent minimal lumen diameter (MLD) and in-segment percent diameter stenosis, the half-dose Synergy device performed better than the permanent-polymer EES, while the 2 endpoints were comparable between full-dose Synergy and Promus Element (table 2).

Table 2. Six-Month Angiographic Endpoints

^a P value for noninferiority.

Citing multiple other studies, Dr. Meredith and colleagues observe that “collectively, these results suggest that the efficacy of the Synergy stent is comparable to that of established durable polymer as well as newer-generation bioabsorbable polymer and bioabsorbable stent platforms delivering limus-based antiproliferative drugs.”

A Step in the Right Direction 

In a telephone interview with TCTMD, Stephen G. Ellis, MD, of the Cleveland Clinic (Cleveland, OH), said EVOLVE is best viewed in the context of growing evidence for a number of bioabsorbable DES technologies. He noted that with 4-year data from the LEADERS trial (Stefanini GG, et al. Lancet. 2011;378:1940-1948), the biolimus-eluting Biomatrix Flex stent (Biosensors International, Morges, Switzerland), is perhaps furthest along in terms of clinical science.

Nonetheless, EVOLVE “is a small step in the right direction,” he said. But the real focus should be on safety rather than efficacy, he added, and although no safety signals have emerged thus far, “you need long follow-up and lots of patients” to be sure. Moreover, he commented, “It’s too early to lump all the biodegradable products in the same category and say, ‘If one’s okay, they’re all okay.’”

Dual Antiplatelet Therapy: Shorter—But Not Too Short

As for the possibility that bioabsorbable-polymer stents might permit abbreviated dual antiplatelet therapy, Dr. Ellis said, “That’s a moving target, because even the more recent studies [looking at] second-generation DES with biostable polymers are suggesting that 6 months may be enough. It would not be unreasonable to think that you might be able to withdraw dual antiplatelet therapy somewhere around 6 months with this product, but that has to be tested.”

Calling the field of bioaborbable-polymer DES a “fascinating technology,” Ron Waksman, MD, of the Washington Hospital Center (Washington, DC), told TCTMD in a telephone interview that the first step was to show that late loss with these devices is equivalent to that of the best permanent-polymer DES on the market, and EVOLVE has passed that test. But the next step is to determine whether bioabsorbable-polymer stents provide greater clinical benefit, and that is more challenging, he observed.

Potential Advantage Only in the Long Run

“[Conventional] second-generation DES are very good, and it’s very hard to beat them with any technology in the short term,” he said. But they continue to show stent thrombosis out to 4 or 5 years, he noted, “so I think if you will see any differential with a biodegradable-polymer technology like Synergy, it will not be in the first year but only at later times.”

Dr. Waksman concluded that the stent field is moving toward biodegradable polymer DES. “It’s nice to see that there are now options [among these innovative devices],” he said.

Dr. Ellis reported that a 1,800-patient US pivotal trial of Synergy vs. Promus Element, with a factorial design involving dual antiplatelet therapy, is slated to begin enrollment before the end of the year.

Meanwhile, the EVOLVE trial data will be used to support CE mark approval for Synergy in Europe, Boston Scientific chief medical officer Keith D. Dawkins, MD, said in a press statement.

Related Stories:

1. Second Generation of Everolimus-Eluting Bioaborbable Stent Shows Promise
2. Long-term Outcomes Improved with Biodegradable Biolimus-Eluting Stent vs. Permanent Polymer SES