SEAS apart: no role for lipid lowering in aortic valve disease

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Calcific aortic stenosis shares risk factors with coronary heart disease and predicts death and MI without the need for large gradients.  Hyperlipidaemia has been suggested as a risk factor for the development of aortic stenosis but to date lipid lowering studies have demonstrated conflicting results.

The SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) trial was a randomised, double blind trial involved 1873 asymptomatic patients with mild to moderate aortic stenosis.  Patients received either 40mg of simvastatin + 10mg ezetimibe (n=943) or placebo (n=929) daily.  The primary outcome was a composite of major cardiovascular events, including death from cardiovascular causes, aortic valve replacement, non-fatal myocardial infarction, hospital admission with unstable angina, heart failure, coronary artery bypass grafting (CABG), PCI or non-haemorrhagic stroke.

Follow up was for a median of 52.2 months with the primary outcome occurring in 333 (35.3%) of the simvastatin-ezetimibe group and 355 (38.2%) in the placebo group (hazard ratio 0.96, 95% CI 0.83-1.12, p=0.59). There was no significant difference in the number of aortic valve replacements between the 2 arms although fewer patients had ischaemic cardiovascular events in the simvastatin-ezetimibe arm (148 patients) than in the placebo arm (187 patients) (hazard ratio 0.78, 95%CI 0.63-0.97, p=0.02). This was predominantly due to a reduction in the number of patients undergoing CABG.  Of concern, cancer occurred more frequently in the simvastatin-ezetimibe group (105 vs 70, p=0.01).

Thus no evidence exists to date that cholesterol lowering can be used to treat aortic valve disease in any way.  The finding of an increased number of cancer cases has prompted a review of cancer cases in the two ongoing ezetimibe trials (SEARCH and IMPROVE-IT), although it is likely to be a chance association.

  • Rossebo AB, Pedersen TR, Boman K etal. Intensive Lipid Lowering with Simvastatin and Ezetimibe in Aortic Stenosis. N Engl J Med 2008;359:1343-56
  • Otto CM (ed). Calcific Aortic Stenosis – Time to Look More Closely at the Valve. N Engl J Med 2008;359:1395-8

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