麻豆传媒

CHICAGO -- Head-to-head comparisons between three drug-eluting stents (DES) suggested that biodegradable polymers do not make for better long-term outcomes, researchers showed in ISAR-TEST (Intracoronary Stenting and Angiographic Results: Test Efficacy of 3 Limus-Eluting Stents) 4.

Compared with the durable-polymer Xience and biodegradable-polymer Yukon Choice devices, the first-generation, durable-polymer Cypher stent performed the worst as its 10-year rate of major adverse cardiovascular events (MACE: all-cause death, myocardial infarction, and target lesion revascularization) exceeded 50% whereas the other two kept rates under 50% (P=0.003).

Yet there was no difference in this regard between Xience and Yukon Choice stents (HR 1.04, 95% CI 0.87-1.24), according to Sebastian Kufner, MD, of Deutsches Herzzentrum München in Germany, reporting the at a late-breaking trial session during the American Heart Association annual meeting here. The study was also published simultaneously online in .

Cypher's poor performance was driven by an uptick in all-cause death (31.8% for Yukon Choice versus 30.3% for Xience versus 37.2% for Cypher, P=0.02). Definite stent thrombosis was also most common after Cypher placement (2.4% versus 1.1% for Yukon Choice versus 0.8% for Xience, P=0.03).

"New-generation DES are superior to early-generation DES in terms of clinical outcomes. The favorable outcome after new-generation DES is driven by increasing event rates over time in patients treated with early-generation DES," Kufner concluded.

Biodegradable-polymer DES have, at best, been shown to be non-inferior to the durable-polymer standard. Many have posited that their benefits can be seen only after the polymer fully degrades over months and years, recalled Sripal Bangalore, MD, MHA, of New York University School of Medicine in New York City, writing in an accompanying editorial in .

With ISAR-TEST 4, however, it appears that there is no real late advantage to biodegradable-polymer DES either, which begs the question of whether paying a high price for them is justifiable, he said.

"The BP-[biodegradable-polymer] DES principle is based on the assumption that converting to a BMS [bare metal stent] is the safest option long-term. However, this assumption has been challenged. Studies have shown long-term persistent low-grade inflammation even with BMS due to metal corrosion and ion leak," Bangalore said.

Kufner and his colleagues from two centers in Munich enrolled patients into ISAR-TEST 4 in 2007 and 2008 (n=2,603). Trial participants were randomized 2:1:1 to the biodegradable-polymer Yukon Choice stent or the permanent-polymer Xience or Cypher stents.

The three arms started off with the same baseline characteristics.

Trial investigators managed to get 10-year outcomes data for just 83% of the cohort, which Bangalore called the "main limitation of the trial."

The trial was also underpowered, commented Roxana Mehran, MD, of Icahn School of Medicine at Mount Sinai and the Cardiovascular Research Foundation in New York City.

It should also be noted, she said, that the Xience is the only device studied in ISAR-TEST 4 that is available in the U.S.; the outdated Cypher is no longer available, and the Yukon is not yet FDA approved.

The data look good for the latter, however, and puts it in line with current-generation DES, Mehran said.

Nonetheless, with even the gold-standard Xience stent accruing MACE at a "staggering rate of ~3.3%/year," it's clear that there is an "urgent need to reduce this persistent risk with improvement in medical therapy and stent technology," Bangalor wrote.

Although outcomes with second-generation DES have plateaued, emerging data suggests that ultra-thin strut design (<70 µm) can bring target lesion failure, myocardial infarction, target lesion revascularization, and stent thrombosis further down, he noted.

"These ultra-thin strut DES also have a biodegradable polymer, but the superior results seen thus far are unlikely to be due to the biodegradable polymer per se given that the outcomes observed are before the polymer fully biodegrades," he said.