Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial

• Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial
  • a randomized, double-blind trial involving 1873 patients with mild-to moderate, asymptomatic aortic stenosis
  • patients received either 40 mg of simvastatin plus 10 mg of ezetimibe or placebo daily
  • primary outcomes was a composite of major cardiovascular events
    • patients 45-85 years at baseline; a median follow-up of 52.2 months
    • simvastatin and ezetimibe did not reduce the composite primary endpoint
    • cancer occurred more frequently in the simvastatin-ezetimibe group (105 vs. 70, P = 0.01)
      • an apparent excess of about one half in the incidence of any new cancer was observed during mean follow-up of approximately 4 years among the 944 patients randomly assigned to ezetimibe plus simvastatin as compared with the 929 randomly assigned to placebo

Notes:

• following the results from SEAS an analysis of data from other ezetimibe trials was undertaken (2):
  • positive aspects of analysis
    • lack of cancer risk from analysis of 2 larger studies
    • SHARP
      • 9264 patients (mean follow-up 2.7 years)
      • patients at least 40 years of age at baseline Simvastatin 20mg/ezetimibe versus placebo
    • IMPROVE-IT
      • 11,353 patients (mean follow-up 1 year)
      • patients at least 50 years of age at baseline
      • simvastatin 40mg/ezetimibe versus simvastatin 40mg
    • no specific increase in a particular type of cancer in SEAS
  • the analysis suggests that:
    • data suggests a 'chance' finding - not a primary end point of any of the studies
    • data from two larger studies does not support findings from SEAS
  • however the data from the SHARP study and IMPROVE-IT study was over a lesser period of exposure to ezetimibe than in SEAS
    • need longer term data from SHARP and IMPROVE-IT to clarify the results further

Reference:

• 1 Rossebo AB et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008 Sep 25;359(13):1343-56.
• 2. Peto R et al. Analyses of cancer data from three ezetimibe trials. N Engl J Med. 2008 Sep 25;359(13):1357-66