Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial

Last reviewed 01/2018

  • 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

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