Biodegradable Polymer Stent No Better Than Xience at 10 Years

November 16, 2018

CHICAGO — Ten-year results from the ISAR-TEST 4 trial have shown that new-generation drug-eluting stents are superior to early-generation stents in terms of clinical outcomes, including mortality.

Other results from this post hoc analysis also showed similar clinical outcomes out to 10 years for two new-generation stents: a biodegradable polymer-based stent and a permanent polymer-based stent.

The 10-year results of ISAR-TEST 4 were presented by Sebastian Kufner, MD, Deutsches Herzzentrum, Munich, at the American Heart Association Scientific Sessions 2018, and simultaneously published online in Circulation.

Designated discussant of the study and author of an accompanying editorial in Circulation, Sripal Bangalore, MD, NYU School of Medicine, New York City, told | Medscape Cardiology that this trial provides information on long-term differences in hard clinical outcomes between the newer second-generation stents and the older first-generation devices.

"Most important is that there was reduction in mortality with both second-generation stents compared to the older stent," he said. "There has been a signal of reduced mortality with these newer stents seen in previous studies and meta-analyses, but the follow-up has been shorter — about 3 to 5 years. This trial adds much longer follow-up."

"To me, it is enforcing what we already suspected but it is good to see consistent results out to 10 years," Bangalore said.

He said these results raise questions about the relevance of some previous trials comparing stents with bypass surgery, such as FREEDOM, which showed a mortality benefit with surgery.

"These trials used older first-generation drug-eluting stents and now, with the modern stents used today, we have to ask whether the mortality benefit with CABG would still be there," he said.

He also pointed out that the "other somewhat surprising result" from this study is the lack of benefit of the biodegradable polymer stent over the permanent polymer stent.

"Previous work has suggested that the polymer containing the drug in drug-eluting stents can itself cause problems, so in the latest biodegradable polymer stents, the polymer gradually disappears after the drug has eluted," he said. This was expected to translate into a long-term reduction in events, but when it was compared with a current-generation durable polymer stent, there was no difference in long-term outcomes, he added.

"We have seen similar results in studies with shorter-term follow-up, and now this has been confirmed in much longer follow-up. This suggests that perhaps the new polymers don't seem to have the same issues as the older ones."

For the ISAR-TEST 4 study, 2603 patients undergoing PCI were randomized to receive treatment in a 2:1:1 ratio with the biodegradable polymer-based sirolimus-eluting stent (Yukon Choice PC, Translumina), the permanent polymer-based everolimus-eluting stent (Xience, Abbott Vascular), or the early-generation permanent polymer-based sirolimus-eluting stent (Cypher, Cordis).

Follow-up at 10 years was available for83% of the study patients.

Results showed that at 10 years, the primary end point of this analysis — major adverse cardiac events (MACE), a composite of death, MI, and target lesion revascularization — was lower with the two new-generation stents than with Cypher, but there was no difference between the two new-generation products. Similar results were seen for mortality.

Definite/probable stent thrombosis was not significantly different among the three groups, but definite stent thrombosis was significantly lower with the two new-generation products than with Cypher. But again, there was no difference between the two newer devices.

ISAR-TEST 4: 10-Year Results
End Point Biodegradable Polymer (Yukon Choice PC), % Permanent Polymer (Xience), % Older Stent (Cypher), %
MACE 47.7 46.0 54. 9
Mortality 31.8 30.3 37.2
Definite/probable stent thrombosis 1.8 2.5 3.7
Definite stent thrombosis 1.1 0.8 2.4


In the Circulation paper, Kufner and colleagues explain that early-generation drug-eluting stent technology showed an excess of adverse events attributable to very late stent thrombosis, and autopsy studies suggest a delay in healing of the stented arterial segment as the underlying issue. New-generation stents have therefore incorporated improvements in backbone alloy, strut thickness, antiproliferative drug, dosage and release kinetics, and more biocompatible polymers.

These improvements translated into enhanced clinical safety and efficacy in comparison with early-generation drug-eluting stents, but these are the first data to look at outcomes beyond 5 years.

They note that the significant reduction in overall MACE with the new-generation drug-eluting stents in this study was driven by significantly lower all-cause mortality.

They further point out that the 18% to 22% relative risk reduction in mortality with the newer stents is only partly explained by the 30% to 50% relative risk reduction in stent thrombosis, and that overall mortality rates in the current study are higher than previously reported in trials with 10-year follow-up.

They suggest that these observations can be explained by a higher mean age and the higher proportion of patients with diabetes in the current study, which might have led to a higher risk for clinically unapparent device-related events, such as silent MI.

On the similar results with the new-generation biodegradable and permanent polymer stents, the authors state: "This suggests that the improvement in polymer biocompatibility with new-generation permanent polymer drug-eluting stents may have resulted in extended safety and efficacy outcomes that are comparable to that of drug-eluting stents where no polymer remains behind over the long term."

Bangalore pointed out that two of the three stents in the ISAR-TEST 4 study are not used routinely in the United States, but even so, he believes the results are still relevant to American clinical practice.

"The Cypher stent was popular years ago but has now been replaced by second generation devices," he explained. "The Xience stent is available and used extensively and the Yukon Choice stent has not been approved in the US, but we do have the everolimus-eluting Synergy biodegradable polymer stent."

He also emphasized that the high overall event rate in the study shows that much more needs to be done for these patients.

"Although the two new-generation stents used in this study showed much better long-term outcomes than the first-generation stent, the 10-year event rate is still very high. After the first year, the MACE rate is 3.3% per year even with these newer stents — this is far too high. We must try to bring this down with improved stent design and better medical therapy," Bangalore said.

"We shouldn't get stuck in the debate over biodegradable versus durable polymer stents — both are good, but not good enough."

The ISAR-TEST 4 study was funded by Deutsches Herzzentrum, and was industry independent. Kufner reports no disclosures. Bangalore is on advisory boards for Abbott Vascular, Biotronik, Amgen, Pfizer; receives research grants from Abbott Vascular and honoraria from Abbott Vascular, Pfizer, AstraZeneca, and Biotronik.

American Heart Association (AHA) Scientific Sessions 2018: Session LBS.06. Presented November 11, 2018.

Circulation. Published online November 11, 2018. Full text, Editorial

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