RESET: Largest Study to Date of Xience, Cypher Shows Noninferiority

PARIS, France—Fresh evidence showing that everolimus-eluting stents (EES) match the efficacy and safety of sirolimus-eluting stents (SES) was presented on Monday, August 29, at the European Society of Cardiology Congress 2011. According to findings from the largest randomized trial yet to compare the 2 stents, the second-generation devices also perform well when used in patients with insulin-dependent diabetes.

For the Randomized Evaluation of Sirolimus-eluting versus Everolimus-eluting stent Trial (RESET), Takeshi Kimura, MD, of Kyoto University Graduate School of Medicine (Kyoto, Japan), and colleagues enrolled over 3,000 low- to moderate-risk patients slated for PCI with DES at 100 Japanese centers between February 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). 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).

RESET evaluated 2 co-primary endpoints: TLR at 12 months and in-segment late loss at 8 to 12 months. EES met noninferiority criteria compared with SES for both endpoints (table 1).

Table 1. RESET: Primary Endpoints

12 Month Follow-up

EES

SES

P for Noninferiority

TLR

4.3%

5.0%

< 0.0001

In-Segment Late Loss, mm

0.07

0.03

< 0.0001


Moreover, the rates of death, MI, and definite or probable stent thrombosis also were similar between the 2 groups.

Prespecified subgroup analyses found that patients with insulin-treated diabetes were less prone to TLR after EES vs. SES use (5.4% vs. 12.3%; HR 0.42; 95% CI 0.18-0.9; P = 0.03), but the same pattern was not seen in patients with non-insulin-treated diabetes (HR 1.03; 95% CI 0.6-1.77; P = 0.92). As such, diabetic patients overall had similar rates of TLR regardless of stent type (5.2% with EES vs. 6.6% with SES; P = 0.24).

What to Do Without Cypher?

To put the results in context, Dr. Kimura clarified that RESET subjects were not very high risk, apart from the subgroup with insulin-treated diabetes, which raises the likelihood of stent thrombosis. Moreover, widespread use of intravascular ultrasound guidance (81%) and dual antiplatelet therapy at 1 year (> 85%) may have affected outcomes, he said.

He also cautioned that the current trial results cannot “provide guidance regarding the selection of coronary DES in clinical practice,” because of the recent announcement that Cypher would be taken off the market. At a press conference, he said of the decision: “This was very unexpected, but sirolimus is losing its patent soon, so there would probably be some other SES available in some other countries, which may be of practical relevance.”

Because low event rates might make it difficult to demonstrate clinically meaningful differences in TLR rates among low-risk patients in head-to-head DES trials, future studies “should focus on more complex patients, in whom coronary artery bypass grafting could be a reasonable alternative,” Dr. Kimura advised.

Looking Ahead to Longer Follow-up, Technological Advances

Following Dr. Kimura’s presentation, discussant Stephan Windecker, MD, of Bern University Hospital (Bern, Switzerland), outlined the clinical implications of RESET.

Dr. Windecker first noted several differences between Japanese and European patients that might affect outcomes. “In Japan, there is a lower rate of acute coronary syndromes and a lower rate of smoking,” he said, adding that the CYP2C19*2 allele, which negatively affects clopidogrel response, is more prevalent in Japanese.

While the current results show no significant advantage for EES in terms of definite stent thrombosis, Dr. Windecker said, combined data from studies including RESET indicate the newer stent imparts a 49% relative risk reduction compared with SES. “Whether the risk of very late stent thrombosis is lower with EES requires confirmation in larger patient populations with longer duration follow-up,” he proposed.

In short, Dr. Windecker concluded, “Everolimus is at least as effective as sirolimus. Although there were no differences in deaths or myocardial infarction up to 1 year later, it has a more deliverable stent form, resulting in a higher procedural success rate.”

Unresolved issues include pinpointing the lowest drug dose that would result in maximal DES efficacy and exploring the long-term performance of EES through the use of biodegradable polymers and bioabsorbable vascular scaffolds, he added.

 


Source:
Kimura T. RESET: One-year outcome of the Randomized Evaluation of Sirolimus-eluting versus Everolimus-eluting stent Trial. Presented at: European Society of Cardiology Congress; August 29, 2011; Paris, France.

 

 

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Disclosures
  • The RESET trial was sponsored by Abbott Vascular.
  • Dr. Kimura reports having served on the scientific advisory boards for and receiving honoraria from Abbott Vascular, Cordis, and Terumo Company.
  • Dr. Windecker reports having received research grants from Abbott, Biosensors, Biotronik, Boston Scientific, Cordis, and Medtronic.

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