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Effect Modifications of Lipid-Lowering Therapy on Progression of Aortic Stenosis (from the Simvastatin and Ezetimibe in Aortic Stenosis [SEAS] Study)
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
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2018 (English)In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 121, no 6, p. 739-745Article in journal (Refereed) Published
Abstract [en]

Observational studies indicate that low-density lipoprotein (LDL) cholesterol acts as a primary contributor to an active process leading to aortic stenosis (AS) development. However, randomized clinical trials have failed to demonstrate an effect of lipid lowering on impeding AS progression. This study explored if pretreatment LDL levels and AS severity altered the efficacy of lipid-lowering therapy. The study goal was evaluated in the analysis of surviving patients with baseline data in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial of 1,873 asymptomatic patients with mild-to-moderate AS. Serially measured peak aortic jet velocity was the primary effect estimate. Linear mixed model analysis adjusted by baseline peak jet velocity and pretreatment LDL levels was used to assess effect modifications of treatment. Data were available in 1,579 (84%) patients. In adjusted analyses, lower baseline peak aortic jet velocity and higher pretreatment LDL levels increased the effect of randomized treatment (p >= 0.04 for interaction). As such, treatment impeded progression of AS in the highest quartile of LDL among patients with mild AS at baseline (0.06 m/s per year slower progression vs placebo in peak aortic jet velocity, 95% confidence interval 0.01 to 0.11, p = 0.03), but not in the 3 other quartiles of LDL. Conversely, among patients with moderate AS, there was no detectable effect of treatment in any of the pretreatment LDL quartiles (all p In conclusion, in a non prespecified post hoc analysis, the efficacy of lipid-lowering therapy on impeding AS progression increased with higher pretreatment LDL and lower peak aortic jet velocity (SEAS study: NCT00092677). 

Place, publisher, year, edition, pages
Elsevier, 2018. Vol. 121, no 6, p. 739-745
National Category
Cardiac and Cardiovascular Systems
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URN: urn:nbn:se:umu:diva-146569DOI: 10.1016/j.amjcard.2017.12.011ISI: 000428102100012PubMedID: 29361285OAI: oai:DiVA.org:umu-146569DiVA, id: diva2:1205944
Available from: 2018-05-15 Created: 2018-05-15 Last updated: 2018-06-09Bibliographically approved

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Boman, Kurt

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