Randomized Evaluation of Sirolimus-eluting versus Everolimus-eluting stent Trial - RESET

Description:

Although numerous studies have outlined the benefit of so-called “second-generation” stents such as Xience V (everolimus-eluting stent [EES]) over the Taxus (paclitaxel-eluting stent) stent (so-called “first-generation”), it is unclear if Xience V is truly superior to the other “first-generation” stent: Cypher (sirolimus-eluting stent [SES]). The current trial sought to compare the relative efficacies of the Xience V and Cypher stents for target lesion revascularization (TLR) at 12 months.

Hypothesis:

Xience V would be noninferior to SES for TLR at 12 months in Japanese patients undergoing drug-eluting stent (DES) percutaneous coronary intervention (PCI).

Study Design

  • Blinded
  • Parallel
  • Placebo Controlled
  • Randomized
  • Stratified

Patient Populations:

Number of screened applicants: 2,697
Number of enrollees: 3,197
Duration of follow-up: 1 year
Mean patient age: 69
Percentage female: 23%

Primary Endpoints:

  • Efficacy: TLR at 1 year
  • Safety: All-cause death/MI at 3 years

Secondary Endpoints:

  • TVR at 12 months
  • All-cause mortality at 12 months
  • MI at 12 months
  • Stent thrombosis

Drug/Procedures Used:

Patients were randomized in a 1:1 fashion to PCI with either Xience V or Cypher Select-plus DES. Stratification was by center, diabetes, and participation in imaging substudies.

Concomitant Medications:

Heparin was used as the anticoagulant of choice during PCI. Statins (77%), beta-blockers (38%), angiotensin-converting enzyme inhibitor/angiotension-receptor blocker (62%). Dual antiplatelet therapy was continued for at least 3 months (87% received clopidogrel, 13% received ticlopidine).

Principal Findings:

A total of 3,197 patients were randomized at 100 centers in Japan, 1,597 to EES and 1,600 to SES. Baseline characteristics were fairly similar between the two arms. About 45% had diabetes mellitus, 11% had history of prior stroke, 30% had prior myocardial infarction (MI), 50% had undergone prior PCI, and 5% prior coronary artery bypass grafting (CABG). Presentation was acute MI in 6%, unstable angina in 12%, and stable angina in the majority. Multivessel coronary artery disease was noted in 47%; 11% underwent multivessel PCI. The median SYNTAX score was 10. Left anterior descending artery PCI was performed in 43% of the patients, and left main trunk in 2%. The mean number of treated lesions was 1.2, with a total stent length of about 31.2 mm per patient. Bifurcation disease was noted in 40% (two-stent strategy in 1%), and chronic total occlusion PCI in 6%; only 0.5% of PCIs were in saphenous vein grafts. Intravascular ultrasound was frequently used (82%), and direct stenting was used in about a quarter of the lesions. The mean reference vessel diameter was 2.6 mm. Overall PCI success rate was 97%. Procedural success was higher in the EES arm (97.8% vs. 96.6%, p = 0.04).

The primary endpoint of TLR at 12 months was similar between EES and SES (4.3% vs. 5.0%, hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.61-1.18, p for noninferiority < 0.0001, p for superiority = 0.34). Target vessel revascularization (TVR) rates were also similar (6.9% vs. 6.9%, p = 0.93). Other endpoints including all-cause mortality (1.9% vs. 2.5%, p = 0.23), MI (3% vs. 3.5%, p = 0.42), and definite/probable stent thrombosis (0.32% vs. 0.38%, p = 0.77) were also similar.

In the subset of patients undergoing angiographic follow-up, in-segment late loss at 8 months was similar (0.06 mm vs. 0.02 mm, p for noninferiority < 0.0001, p for superiority = 0.24).

Interpretation:

The results of the current trial indicate that in Japanese patients undergoing PCI, EES is noninferior to SES for TLR at 12 months, with no difference in clinical endpoints, including stent thrombosis. 

These results, while interesting, are somewhat moot, since the production of Cypher DES was discontinued earlier this year in the United States. Moreover, several large trials have provided longer-term follow-up with EES and SES stents. Further stent trials/registries should also focus on PCI in high-risk patients and complex lesions to provide a better understanding of the choice of one stent versus another for various scenarios.

References:

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;Jul 23:[Epub ahead of print].

Presented by Dr. Takeshi Kimura at the European Society of Cardiology Congress, Paris, France, August 2011.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Aortic Surgery, Cardiac Surgery and SIHD, Interventions and Coronary Artery Disease, Chronic Angina

Keywords: Japan, Coronary Artery Disease, Myocardial Infarction, Stroke, Follow-Up Studies, Pyridinolcarbamate, Angina, Stable, Drug-Eluting Stents, Sirolimus, Percutaneous Coronary Intervention, Paclitaxel, Registries, Thrombosis, Saphenous Vein, Confidence Intervals, Coronary Artery Bypass, Diabetes Mellitus


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