IVUS Supports Effectiveness of Novel Stent with Bioabsorbable Polymer

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Compared with a standard drug-eluting stent (DES), a novel sirolimus-eluting stent featuring micro-reservoirs and a biodegradable polymer provides significantly better suppression of neointimal obstruction as assessed by intravascular ultrasound (IVUS). The study was published online March 8, 2011, ahead of print in Circulation: Cardiovascular Interventions.

Researchers led by Yasuhiro Honda, MD, of Stanford University (Stanford, CA), conducted an IVUS substudy of patients in the NEVO ResElution-I trial (Res-I).

The original trial enrolled 394 patients at 40 sites and randomized them to the Nevo sirolimus-eluting stent (Cordis, Bridgewater, NJ) or the Taxus Liberté paclitaxel-eluting stent (Boston Scientific, Natick, MA). The first 50 patients in each treatment arm at selected study sites were predefined for inclusion in the IVUS substudy.

In addition to standard IVUS variables, uniformity of neointimal distribution within stents was evaluated in 3 dimensions by computing mean neointimal thickness within 12 equally spaced radial sectors on every 1-mm cross section along the stented segment.

Less Neointimal Proliferation, Cross-Sectional Narrowing

Nevo is a balloon-expandable cobalt chromium alloy stent containing multiple reservoirs filled with a blend of sirolimus and a bioabsorbable polymer. Absorption of both drug and polymer occurs within about 3 months, leaving only a biologically inert bare-metal platform.

A total of 73 patients had 6-month IVUS follow-up available for analysis. Overall, Nevo resulted in less percent neointimal obstruction compared with Taxus, with less maximum percent cross-sectional narrowing. In addition, the absolute variability of neointima distribution, assessed by the standard deviation (SD) of neointimal thickness within each stent, was reduced with Nevo (table 1).

Table 1. Neointimal Proliferation at 6 Months

Nevo also showed significantly less lumen volume loss and minimum lumen area loss compared with Taxus. Moreover, Nevo was associated with less positive vessel remodeling, with changes in vessel volume index of 0.36 ± 0.63 mm³/mm vs. 1.30 ± 1.36 mm³/mm for Taxus (P = 0.003).

At 6 months, there were no significant differences between the 2 stent groups in the rates of MI, TVR, target lesion failure, or MACE. While no stent thromboses were observed in the Nevo group, 1 case of Academic Research Consortium-defined probable stent thrombosis occurred in the Taxus group.

According to Dr. Honda and colleagues, the IVUS substudy results match those of the larger angiographic trial that demonstrated superiority of the Nevo stent over Taxus for the primary endpoint of in-stent late loss (0.13 ± 0.31 mm vs. 0.36 ± 0.48 mm; P < 0.001 for noninferiority and superiority).

What Gives Nevo the Edge?

Several factors may contribute to the differing neointimal distribution within stents, the investigators say.

Importantly, the type of drug used affects not only the total amount of neointima but also the pattern of neointimal distribution. Sirolimus and paclitaxel, they write, vary in terms of diffusion capacity and distribution in the vascular wall. Sirolimus distributes equally within the vascular layers, whereas paclitaxel tends to accumulate in the adventitia. Another possible explanation for the more uniform distribution of neointima seen with Nevo is protection of the drug-polymer component in the reservoir during tracking to and across the lesion. Surface-coated stents may be more likely to peel, crack, or wrinkle, thereby reducing the effective distribution of the drug.

Because the bioabsorbable polymer is blended with sirolimus and restricted to the interior of the reservoirs in Nevo, there is less initial contact with the arterial vessel wall. This might limit the polymer-induced arterial wall inflammation that is thought to occur with some bioabsorbable stents, thus reducing the risk of stent thrombosis and the need for prolonged dual antiplatelet therapy, Dr. Honda and colleagues conclude.

In a telephone interview with TCTMD, David E. Kandzari, MD, of Piedmont Heart Institute (Atlanta, GA), agreed with this assessment but said the inflammation theory remains hypothetical.

In addition, he said the quick dissolution or resorption of the polymer-drug blend from the stent is likely due to 2 factors:

• Less polymer burden on the stent because the substance is only contained in the reservoirs
• The composition of the polymer itself, which is markedly different from biopermanent polymers on all current DES in the United States

The Next Step

Following the success of Res-I, a second trial called Nevo II was launched in Europe as a multicenter trial of Nevo vs. the everolimus-eluting Xience V stent (Abbott Vascular, Santa Clara, CA). However, enrollment in Nevo II was suspended in late 2010 because of problems with the balloon catheter, Dr. Kandzari reported, adding that the stent itself is not being modified.

“It’s my understanding that once the issues with the stent delivery system are addressed the study will resume, with expectations to bring the Nevo III study to the United States,” said Dr. Kandzari, who will be the coprincipal investigator of the planned trial.

He also pointed out that although Nevo arose from the Conor stent, which failed to meet its primary endpoint in the COSTAR II trial, the newer model is an entirely different device except for its reservoir technology.

“This is important because many clinicians perceive that the Conor stent was not clinically successful in COSTAR II and [believe] that this may translate into challenges or issues related to the Nevo platform,” Dr. Kandzari said. “But the Nevo uses a different drug and an entirely different drug-elution kinetic.”

 

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Source:
Otake H, Honda Y, Courtney BK, et al. Intravascular ultrasound results from the NEVO ResElution-I trial: A randomized, blinded comparison of sirolimus-eluting NEVO stents with paclitaxel-eluting Taxus Liberté stents in de novo native coronary artery lesions. Circ Cardiovasc Interv. 2011;Epub ahead of print.

 

 

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• Second Generation of Everolimus-Eluting Bioabsorbable Stent Shows Promise
• ABSORB: 2-Year Data Show Bioabsorbable Stent Remains Safe, Effective
• COSTAR II Results Published, Taxus Outperforms Conor Stent