Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting - EXCELLENT (EES vs. SES)

Description:

Although second-generation stents such as everolimus-eluting stents (EES) are routinely used, very few randomized data exist that directly compare EES to first-generation stents such as sirolimus-eluting stents (SES). The EXCELLENT trial sought to compare outcomes after EES and SES implantation in a real-world population of patients presenting with coronary artery disease (CAD).

Hypothesis:

EES would be noninferior to SES in reducing neointimal hyperplasia at 9 months in patients presenting with CAD.

Study Design

  • Randomized
  • Blinded
  • Parallel
  • Factorial
  • Stratified

Patient Populations:

  • >50% stenosis by visual estimation
  • Evidence of myocardial ischemia
  • Stable angina
  • Unstable angina
  • Recent infarction, silent ischemia
  • Positive functional study or reversible changes in the ECG consistent with ischemia
  • Target lesion must be located in a native coronary artery
  • Reference vessel diameter between 2.25 mm and 4.25 mm

    Number of enrollees: 1,443
    Duration of follow-up: 12 months
    Mean patient age: 63 years
    Percentage female: 36%
    Ejection fraction: 61%

Exclusions:

  • Gastrointestinal or genitourinary bleeding ≤3 months, major surgery ≤2 months
  • Hemoglobin <10 g/dl, platelet count <100K
  • Elective surgical procedure planned ≤12 months
  • Left ventricular ejection fraction <25%, or in shock
  • MI ≤72 hours
  • Creatinine level ≥3.0 mg/dl or dependence on dialysis
  • Severe hepatic dysfunction (aspartate aminotransferase [AST], alanine aminotransferase [ALT] ≥x3 upper limit of normal)
  • Patients who had received any stent implantation in the target vessel prior to enrollment
  • Patients with significant left main stenosis
  • Bare-metal stent or drug-eluting stent in-stent restenosis
  • Chronic total occlusion
  • True bifurcation lesions requiring two stents

Primary Endpoints:

  • In-segment late luminal loss at 9 months

Secondary Endpoints:

  • In-stent late luminal loss at 9 months
  • All-cause mortality at 12 months
  • Cardiovascular mortality at 12 months
  • MI at 12 months
  • TLR at 12 months
  • Stent thrombosis at 12 months

Drug/Procedures Used:

Patients were randomized in a 3:1 fashion to either EES (Xience V or Promus) or SES (Cypher Select).

Concomitant Medications:

  • All patients received at least 300 mg of aspirin and 300-600 mg of clopidogrel. Unfractionated heparin was used to maintain an activated clotting time (ACT) of ≥250 seconds.
  • Dual antiplatelet therapy mandated for a minimum of 12 months in both arms
  • Glycoprotein IIb/IIIa inhibitors (1.6%)
  • Statins (83%)
  • Beta-blockers (61%)

Principal Findings:

A total of 1,443 patients were randomized, 1,079 to EES and 364 to SES. Baseline characteristics were fairly similar between the two arms. About 38% had diabetes, and 9% had undergone prior percutaneous coronary intervention (PCI). About 52% of patients presented with acute coronary syndromes, including 3% with ST-elevation myocardial infarction (STEMI). The left anterior descending artery was the target vessel in about 50% of the patients. Multivessel disease was noted in about 52% of the patients, and 11% were bifurcation lesions. The mean number of stents used per patient was 1.6, with a mean stented length of about 28 mm per lesion. Intravascular ultrasound was used in about 44% of the patients. The minimal in-segment luminal diameter (MLD) at baseline was 2.22 mm.

At 9 months, the primary endpoint of in-segment late luminal loss was similar between the EES and SES arms, and met the predefined criteria for noninferiority (0.11 vs. 0.06 mm, p for noninferiority = 0.038). Similarly, in-stent late loss was also similar (0.19 vs. 0.15 mm, p for noninferiority = 0.012). Clinical outcomes at 12 months, including target lesion revascularization (TLR) (2.4% vs. 1.7%, p = 0.39), all-cause mortality (0.7% vs. 1.1% p = 0.48), MI (1.4% vs. 1.4%, p = 0.98), cardiac death or MI (2.1% vs. 2.5%, p = 0.63), and definite or probable stent thrombosis (0.4% vs. 0.8%, p = 0.38) were similar between the EES and SES arms, respectively. No significant interactions in various subgroups tested were noted.


Interpretation:

The results of the EXCELLENT trial in patients with CAD from South Korea indicate that EES is noninferior to SES in inhibiting late lumen loss at 9 months and clinical outcomes including stent thrombosis at 12 months. This trial adds to recently presented data from ISAR-TEST-4 and SORT OUT IV comparing EES to SES, which also demonstrated similar outcomes between EES and SES. Further long-term follow-up data and cost-effectiveness analyses are awaited.

References:

Park KW, Chae IH, Lim DS, et al. Everolimus-Eluting Versus Sirolimus-Eluting Stents in Patients Undergoing Percutaneous Coronary Intervention: The EXCELLENT (Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting) Randomized Trial. J Am Coll Cardiol 2011;58:1844-1854

Presented by Dr. Hyo-Soo Kim at the Transcatheter Cardiovascular Therapeutics Meeting (TCT 2010), Washington, DC, September 25, 2010.

Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Atherosclerotic Disease (CAD/PAD), Interventions and ACS, Interventions and Coronary Artery Disease, Chronic Angina

Keywords: Coronary Artery Disease, Myocardial Infarction, Republic of Korea, Acute Coronary Syndrome, Follow-Up Studies, Angina, Stable, Immunosuppressive Agents, Constriction, Pathologic, Electrocardiography, Sirolimus, Hyperplasia, Percutaneous Coronary Intervention, Stents, Thrombosis, Diabetes Mellitus


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