RESET Published: Comparable Efficacy, Safety with EES, SES at 1 Year

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In patients with stable coronary artery disease (CAD), the use of either everolimus-eluting stents (EES) or sirolimus-eluting stents (SES) results in low rates of both target lesion revascularization (TLR) and stent thrombosis at 1 year, according to randomized trial results published online July 23, 2012, ahead of print in Circulation.

Early results from the trial were first presented at the European Society of Cardiology Congress 2011 in Paris, France.

For the Randomized Evaluation of Sirolimus-eluting versus Everolimus-eluting stent Trial (RESET), investigators led by Takeshi Kimura, MD, of Kyoto University Graduate School of Medicine (Kyoto, Japan), enrolled 3,197 low- to moderate-risk CAD patients (including 3,927 lesions) slated for PCI with DES at 100 Japanese centers between February 2010 and July 2010. Subjects were randomly assigned to receive either Xience V EES (n = 1,597; Abbott Vascular, Santa Clara, CA) or Cypher SES (n = 1,600; Cordis/Johnson & Johnson, Bridgewater, NJ).

Noninferiority Proven

At 1 year, TLR, the primary efficacy endpoint, occurred in 65 patients in the EES group, and in 76 patients in the SES group, demonstrating noninferiority but not superiority of EES to SES. In an angiographic substudy (n = 482) of those undergoing follow-up angiography between 240 and 365 days after the index PCI, the primary endpoint of in-segment late loss also was indicative of noninferiority of EES relative to SES, but not superiority. In addition, the cumulative incidence of definite stent thrombosis was low and similar between the 2 groups (table 1).

Table 1. One-Year Outcomes

The rates of death, MI, and definite or probable stent thrombosis also were similar between the 2 groups. Interestingly, there was a trend toward lower rates of TLR in EES patients than in SES patients in the subgroup with insulin-dependent diabetes (P for interaction = 0.07) as well as those with multivessel PCI (P for interaction = 0.15).

Questions Remain

According to the study authors, the results of RESET are consistent with previously reported randomized trials comparing EES with SES suggesting similar efficacy and safety outcomes. But at least 2 trials with angiographic primary endpoints reported lower binary restenosis rates for EES vs. SES and 1 trial (LONG-DES-III) suggested greater in-segment late loss with EES.

They add that questions remain regarding the efficacy of EES in patients with complex anatomic characteristics as evaluated by the Syntax score. “However, early restenosis leading to repeated revascularization in anatomically complex patients is still an issue to be addressed in contemporary PCI using DES, which has been clearly demonstrated in the SYNTAX trial,” the study authors note.

Furthermore, they say the trend toward lower rates of TLR among EES subgroups coupled with a recent observational study comparing EES with a historical control SES group suggesting a lower 3-year risk for TVR with EES adds support for the “possibility of superior anti-restenostic efficacy of EES.” Still, the study authors caution that “future head-to-head DES trials [should] focus more on complex patients such as those in whom CABG could be a reasonable alternative.”

Cypher Has Left the Ring, but Sirolimus Still a Contender

In a telephone interview with TCTMD, David E. Kandzari, MD, of the Piedmont Heart Institute (Atlanta, GA), pointed out that since Cypher is no longer manufactured, DES trials including the stent are clinically moot.

“Although [RESET] shows that EES is as good as SES, maybe we should be asking for something better,” he said. “Because the bottom line is that at least in a direct head-to-head comparison, while [EES] look to be as good as what has been our ‘gold standard’ for over 10 years, it really has not convincingly demonstrated superiority.”

In general, Dr. Kandzari said the study shows EES as a “suitable standard for comparison or as a benchmark for new types of DES.” And, while there is little reason to continue to study Cypher itself, there is reason to consider the use of sirolimus, now generic, in other stent platforms given that it has held its own for so many years against competing DES, he observed.

When Cordis announced plans to discontinue the stent in June 2011, the company also said it would no longer pursue the development of another SES. But Dr. Kandzari said the efficacy and safety of sirolimus cannot be argued and predicted that it will be a contender in the development of future DES.

“Sirolimus has a very wide therapeutic window and it has a wide safety window as well,” he said. “You can cut the dose in half and still get pretty much the same outcome, and you can double the dose without creating a lot of vessel toxicity or inflammation. In contrast, you cannot do that with paclitaxel, for example, without getting tissue necrosis and cell death, and you cannot reduce the dose without rendering [the DES] basically inert. So, sirolimus permits wider ranges in dosing and that is something that is very attractive going forward and looking toward bioabsorbable stents, bioabsorbable polymers and things of that nature.”

Study Details

Baseline characteristics were largely similar between groups in the all-comers trial, the main exception being prior CABG, which was higher in SES than in EES patients (6.2% vs. 3.9%; P = 0.003). The study population included large proportions of patients with advanced age, diabetes, multivessel CAD, and prior PCI, and significant proportions of patients with heart failure, hemodialysis, left main coronary artery disease, small vessel disease, chronic total occlusion, and bifurcation lesions.

 

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Source:
Kimura T, Morimoto T, Natsuaki M, et al. Comparison of everolimus-eluting and sirolimus-eluting coronary stents: 1-year outcomes from the randomized evaluation of sirolimus-eluting versus everolimus-eluting stent trial (RESET). Circulation. 2012;Epub ahead of print.

 

 

Related Stories:

• Xience V Noninferior to Cypher for Primary PCI
• Xience Shows Noninferior Late Loss to Cypher, Similar Hard Outcomes
• RESET: Largest Study to Date of Xience, Cypher Shows Noninferiority