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At 3 years, real-world patients treated with a biodegradable-polymer limus-eluting stent fare as well as—but no better than—those who receive permanent-polymer drug-eluting stents (DES), according to data published in the September 20, 2011, issue of the Journal of the American College of Cardiology.

The findings are the latest update from the randomized ISAR-TEST 4 (Intracoronary Stenting and Angiographic Results: Test Efficacy of 3 limus-eluting STents) trial.

For the all-comers study, investigators led by Robert A. Byrne, MB, BCh, of the Deutsches Herzzentrum (Munich, Germany), randomized 2,603 CAD patients at 2 German clinics to sirolimus-eluting biodegradable-polymer stents (microporous stainless steel platform by Translumina, Hechingen, Germany; n = 1,299) or permanent-polymer DES (n = 1,304), including sirolimus-eluting Cypher stents (Cordis, Miami Lakes, FL) and everolimus-eluting Xience V stents (Abbott Vascular, Abbott Park, IL). Baseline and lesion characteristics were well balanced among the various comparison groups.

No Difference in Primary Endpoint

At 3-year follow-up, there was no difference in the incidence of the primary endpoint (composite of cardiac death, target vessel-related MI, or TLR) between the biodegradable- and permanent-polymer DES, a finding that held true across prespecified subgroups including age (up to 67.6 years vs. older), sex, diabetes status, and vessel size (at least 2.73 mm vs. smaller). TLR and death or MI rates were also similar between the treatment arms, while rates of Academic Research Consortium-defined definite or probable stent thrombosis were low and comparable (table 1).

Table 1. Three-Year Outcomes: Biodegradable- vs. Permanent-Polymer DES

 
In a secondary comparison, patients assigned to the permanent-polymer cohort were randomized to Xience (n = 652) or Cypher (n = 652). Again, both treatment groups showed similar results (table 2).

Table 2. Three-Year Outcomes: Xience vs. Cypher

 
Although definite or probable stent thrombosis occurred somewhat less frequently in patients receiving the biodegradable-polymer DES, the difference was not significant because the overall incidence was quite low, the authors note.

Will Longer Follow-up Make a Difference?

According to Dr. Byrne and colleagues, the rarity of events is “an ongoing issue in trials of emerging DES technology, making the design of trials powered to detect [a] safety benefit with comparator stents largely infeasible. In time, however, aggregate long-term data from completed or ongoing biodegradable polymer trials might conceivably shed some light on this question.”

Another strategy for ferreting out differences between stent technologies is performing a meta-analysis, and in fact a study presented by Dr. Byrne on May 20 at EuroPCR 2011 in Paris, France, showed positive safety outcomes. A 3-year meta-analysis of 3 randomized trials comparing biodegradable- and permanent-polymer stents, ISAR-TEST 3, ISAR-TEST 4, and LEADERS, demonstrated a reduction in the primary endpoint and definite stent thrombosis, although no difference in definite/probable stent thrombosis.

The current study does have certain strengths, Dr. Byrne and colleagues emphasized. Broad inclusion criteria and a wide range of patient and lesion complexities mean that the findings are likely to be generalizable. Furthermore, 3-year follow-up captures relatively late-occurring events.

On the downside, they acknowledge, the secondary comparison between Xience and Cypher was underpowered. In addition, prespecified angiographic follow-up may have influenced the rates of the individual components of the primary endpoint. Another limitation is that although 6 months of dual antiplatelet therapy was recommended for all patients, data on the actual duration of such therapy are not available.

Glass Half Full or Half Empty?

“There are 2 ways to look at these data,” David E. Kandzari, MD, of the Piedmont Heart Institute (Atlanta, GA), told TCTMD in a telephone interview. “One would be to say that an experimental bioresorbable polymer stent, with all the uncertainties surrounding [the effectiveness of] bioresorption, fares as well angiographically and clinically as both a contemporary permanent polymer stent and the oldest DES, which serves as a reference standard.

“But the other way to look at the data is to say that the bioresorbable stent was no better than a permanent polymer DES,” he continued. “So from a patient-oriented, outcomes perspective, these results challenge a longstanding assumption in the interventional community that whatever is newer is going to be better.”

Moreover, the overall long-term results are very favorable for all DES—likely due in part to synergy with improved medical therapy, Dr. Kandzari noted. In particular, the low rates of stent thrombosis with Xience are consistent with other trials, he added.

According to Dr. Kandzari, this raises the issue: Is there truly a need for a biodegradable polymer or even a completely resorbable stent at all? If so, one would have expected to see at least some signal of late safety differences with permanent-polymer DES by 3 years, he commented.

Potential for Shorter Antiplatelet Therapy 

Dr. Kandzari stressed, though, that there are potential advantages to bioabsorbable stents that were not addressed in this trial. Probably the most clinically relevant, he said, is the possibility that these designs, with their presumed more rapid healing, may allow abbreviated dual antiplatelet therapy. Answering that question, however, requires prospective testing in a large population.

“Meanwhile, I think we’ll continue to see innovation in the field,” Dr. Kandzari said. “And my expectation is that, rather than transitioning directly to completely bioresorbable stents or nonpolymeric stents, biodegradable-polymer designs will be the next iteration introduced into the marketplace.”

Nonetheless, he underlined, “this trial reminds us that we still need proof [of safety and efficacy], so that adoption will not be based simply on intuition.”

With the exit of Cypher from the market, the comparison with Xience no longer carries much weight, Dr. Kandzari pointed out. But, scientifically, it shows that the older stent can stand up as a reference point for future stent designs. In future stent trials, however, the comparator for new DES designs is likely to be Xience or perhaps the zotarolimus-eluting Resolute with a biocompatible polymer (Medtronic, Minneapolis, MN), he predicted.

 

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Source:
Byrne RA, Kastrati A, Massberg S, et al. Biodegradable polymer versus permanent polymer drug-eluting stents and everolimus- versus sirolimus-eluting stents in patients with coronary artery disease: 3-year outcomes from a randomized clinical trial. J Am Coll Cardiol. 2011;58:1325-1331.

 

 

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• Biodegradable Polymer DES Proves Safe, Effective vs. Other Polymer Strategies