Solid Four-Year Safety and Efficacy Data With Biodegradable-Polymer DES

March 30, 2012

March 30, 2012 (Chicago, Illinois) — New long-term data from a combined analysis of trials, including patients treated with drug-eluting stents with a biodegradable polymer, shows that the new stents reduce the risk of stent thrombosis and target lesion revascularization (TLR) compared with a first-generation drug-eluting stent (Cypher Select, Cordis) [1].

Treatment with the biodegradable-polymer drug-eluting stents significantly reduced the risk of TLR 18% and stent thrombosis 44% compared with the Cypher stent, with the reduction in stent thrombosis driven by a significant 78% reduction in the risk of very late stent thrombosis.

The pooled analysis combines data from three randomized trials of stents with biodegradable polymers: ISAR-TEST-3 and ISAR-TEST-4, both of which studied the Yukon Choice PC stent (Translumina Therapeutics), and the Limus Eluted from a Durable versus Erodable Stent Coating (LEADERS) study of the biolimus-eluting Biomatrix Flex stent (Biosensors International). In all, 2358 patients received a biodegradable-polymer stent and 1704 received a Cypher stent.

"With biodegradable polymers, the whole concept behind the technology is quite attractive, in terms of reducing late safety events, such as stent thrombosis, but in the individual studies we didn't really see a clear result, even with the relatively long-term follow-up that we published with the ISAR studies and LEADERS trial," Dr Robert Byrne (Deutsches Herzzentrum, Munich, Germany) told heartwire . "When you're looking for differences in these rare safety events, I think you really need to look at a large number of patients."

The results of study were presented earlier this week at the American College of Cardiology (ACC) 2012 Scientific Sessions and published online simultaneously March 24, 2012 in the European Heart Journal.

Following Up on Positive Three-Year Results

At EuroPCR 2011, Byrne presented three-year data showing that the bioerodable polymers were associated with less stent thrombosis and better clinical outcomes than stents with permanent polymers. In that analysis, the composite primary end point, made up of cardiac death, MI, and clinically indicated TLR, occurred in 18.2% of the patients treated with the biodegradable-polymer stents and 20.1% in the permanent-polymer group (hazard ratio [HR] 0.85, p=0.04).

To heartwire , Byrne said the group focused on TLR and stent thrombosis for the four-year analysis "to keep things simple," although their results showed that the reduction in cardiac death, MI, and TLR was maintained at four years (HR 0.85; p=0.027). The safety analysis showed a statistically significant reduction in the risk of stent thrombosis, while the efficacy analysis showed there was a statistically significant reduction in the risk of TLR.

Clinical Outcomes Through Four Years: ISAR-3, ISAR-4, and LEADERS

End point Biodegradable polymer, n=2358 (%) Durable polymer Cypher, n=1704 (%) Hazard ratio (95% CI)
Death 9.3 10.0 0.90 (0.73–1.11)
Cardiac death 5.2 5.9 0.87 (0.66–1.15)
MI 6.0 6.8 0.96 (0.74–1.24)
Definite stent thrombosis 1.3 2.8 0.56 (0.35–0.90)
TLR 12.0 13.7 0.82 (0.68–0.98)
Cardiac death or MI 9.9 11.6 0.89 (0.73–1.09)
Cardiac death, MI, or TLR 19.0 21.6 0.85 (0.74–0.98)

All three studies included a broad range of patients, with LEADERS considered an "all-comers" trial, said Byrne. While ISAR-3 and ISAR-4 investigators excluded patients with left main disease and restenotic lesions, as these individuals were randomized in other trials, such as ISAR-Left Main and ISAR DESIRE, the patients included typically represented the types of patients most clinicians would encounter in clinical practice. "I think this speaks to the generalizability of what we found," said Byrne.

In a landmark analysis examining safety between one and four years, there was a significant 78% reduction in the rate of stent thrombosis, with 0.2% events occurring in the patients treated with the biodegradable-polymer stents and 1.3% occurring in the Cypher-treated patients (HR 0.22; p=0.004).

Regarding comparisons with second-generation stents, Byrne said clinicians will need to be patient with regard to learning how well the biodegradable-polymer drug-eluting stents stack up. Of particular interest will be how well these stents perform against Xience everolimus-eluting stents (Abbott) and the Endeavor Resolute (Medtronic). Those studies are currently ongoing, but there will considerable time before long-term data are available to see how well the biodegradable-polymer drug-eluting stent fares against the newer stents in terms of safety.

"If you asked me, I think biodegradable-polymer drug-eluting stents look like they'll play an increasing role as a workhorse stent in many cath labs around the world," said Byrne. "I suppose whether that happens in the US will depend on the Food and Drug Administration. The other question is whether these stents are just a bridge--are we waiting for the fully bioabsorbable scaffolds to come along? It's interesting speculation, but the biodegradable-polymer stents seem to be a good product, and whether bioabsorbable scaffolds get into day-to-day use in broad, unselected patients and lesions remains an open question. I'd say probably not in the next five years, but maybe 10 years down the line."