麻豆传媒

PARIS -- Taking permanent polymer out of the equation for drug-eluting stents doesn't hurt and may help long-term outcomes, according to a bevy of studies reported here.

Biodegradable polymer and polymer-free stents came out largely equivalent to durable polymer stents in study results reported at the European Society of Cardiology's EuroPCR meeting.

But one study pooling the three largest such trials on biodegradable polymer stents showed reduced clinical event and stent thrombosis rates at three years, Robert A. Byrne, MBBCh, of Technische Universitat in Munich, Germany, and colleagues said.

"For the first time, we're actually seeing a difference in results," Byrne told 麻豆传媒, noting that prior studies have not had the numbers, or the length of follow up, to show a difference up to this point.

"The hypothesized advantages of these stents are over the medium to long term because we think these stents have improved vascular healing, and therefore are going to have reduced stent thrombosis," he explained.

"We've got to be at least as good as the existing stents at the 12-month period in terms of prevention of restenosis and general efficacy. Then you shift the time frame and you look out to three to five years," Byrne added.

Getting rid of the polymer -- either entirely with creative strategies to still deliver drug to the vessel wall without it, or after the drug has been eluted and polymer is no longer needed to deliver it -- has been popular route for next generation drug-eluting stents.

Inflammatory response to polymer residue is suspected as a key factor in delayed arterial healing and late stent thrombosis.

Polymer-Free Stents

One such creative strategy was reported at EuroPCR by Didier Carrie, MD, PhD, of Hôpital de Rangueil in Toulouse, France. The Cre8 stent uses reservoirs on the surface of the stent instead of polymer to hold sirolimus.

In the NEXT study that utilized that stent, late lumen loss as a surrogate endpoint for restenosis was lower with the novel stent than with the durable polymer paclitaxel-eluting Taxus Liberté stent (0.14 versus 0.34 mm at six months which met superiority criteria at P<0.0001) among 323 non-acute randomized patients.

Other six month clinical outcomes, including stent thrombosis, were equal between the two.

A separate study comparing five-year outcomes with a polymer-free sirolimus-eluting stent (Translumina Yukon) and a durable polymer paclitaxel-eluting Taxus stent showed that the equivalent clinical outcomes persisted. Definite stent thrombosis among these 450 stable patients, randomized in the ISAR-TEST study, was numerically less common with the polymer-free stent at five years, but not statistically significant (0.4% versus 1.3%, P=0.32).

But with such low event rates and "with numbers that low, you couldn't really spot significant trends," noted study presenter Lamin A. King, MD, also of Technische Universitat, when explaining the difference between his results and those of Byrne's pooled analysis.

Biodegradable Polymer Stents

The study pooling individual patient data with biodegradable polymer stents across ISAR-TEST 3, ISAR-TEST 4, and LEADERS studies at three years was reported by Byrne at the same late-breaking session.

Those trials randomized a total of 4,052 patients to the first-generation Cypher stent compared with the Yukon stent or the biolimus-eluting Biomatrix Flex stent for the biodegradable arm.

The biodegradable polymer stents halved the rate of definite stent thrombosis at three years compared with the permanent polymer stent (1.2% versus 2.1%, hazard ratio 0.50, P=0.013). In a landmark analysis, this lower risk persisted overall, for events past 30 days, and for very late events past one year (P=0.01 to P=0.02).

The combination of definite and probable stent thrombosis showed a non-significant trend for three-year reduction in risk (hazard ratio 0.68, P=0.11), as did the composite of cardiac death and myocardial infarction, (HR 0.88, P=0.28).

Target lesion revascularization, though, was significantly reduced at three years with the biodegradable polymer stents (12.0% versus 13.2%, HR 0.82, P=0.04).

Thus the primary composite endpoint of cardiac death, MI, and target lesion revascularization favored the biodegradable stents at 18.2% versus 20.1% (HR 0.85, P=0.04).

"This is why we have biodegradable polymers," concluded session co-chair David O. Williams, MD, of Brigham and Women's Hospital in Boston. "We think it makes a difference."

One concern with comparisons to durable polymer stents in trials to date has been that the polymer is not the only factor that differs.

But that question was answered by the NOYA-I study, reported by Run-Lin Gao, MD, of Fu Wai Hospital in Beijing, China, and colleagues at the late-breaking clinical trials session.

That trial compared the sirolimus-eluting FIREBIRD 2 stent popular in China, which uses the same durable polymer as Taxus stents, and the novel Noya stent, which uses an identical backbone and drug, with the exception of a biodegradable polymer.

During nine month follow up of the 300 patients in China randomized to treatment in the trial, in-stent late lumen loss was comparable with the biodegradable polymer stent at 0.11 versus 0.13 mm (P<0.001 for noninferiority).

All clinical endpoints likewise came out equivalent at nine and 12 months between the two stents.

Study discussant Patrick W. Serruys, MD, PhD, of Erasmus Medical Center in Rotterdam, the Netherlands, called these "indisputable results of a noninferiority trial on late loss" but agreed with Gao's group on the need for a large-scale trial.

Altogether the emerging message is one of "evolving evidence that the biodegradable or polymer-free stents appear to have lower rates of late stage thrombosis, which is really the hypothesis," King told 麻豆传媒.