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  1. Alistair Lindsay, Editor

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

Calcific aortic stenosis shares risk factors with coronary heart disease and predicts death and myocardial infarction even before large gradients appear. 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 involving 1873 asymptomatic patients with mild to moderate aortic stenosis. Patients received either 40 mg of simvastatin +10 mg ezetimibe (n = 943) or placebo (n = 929) daily. One patient was not randomised. 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, percutaneous coronary intervention 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 to 1.12, p = 0.59). There was no significant difference in the number of aortic valve replacements between the two 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 to 0.97, p = 0.02). This was predominantly owing to a reduction in the number of patients undergoing coronary artery bypass grafting. 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 such cases in the two ongoing ezetimibe trials (SEARCH and IMPROVE-IT). This analysis has shown an increase in cancer mortality risk in the combined ezetimibe groups, although illogically …

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