University of Oulu

Anders M. Greve, Casper N. Bang, Kurt Boman, Kenneth Egstrup, Y. Antero Kesäniemi, Simon Ray, Terje R. Pedersen, Kristian Wachtell, Relation of Lipid-Lowering Therapy to Need for Aortic Valve Replacement in Patients With Asymptomatic Mild to Moderate Aortic Stenosis, The American Journal of Cardiology, Volume 124, Issue 11, 2019, Pages 1736-1740, ISSN 0002-9149,

Relation of lipid-lowering therapy to need for aortic valve replacement in patients with asymptomatic mild to moderate aortic stenosis

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Author: Greve, Anders M.1; Bang, Casper N.2; Boman, Kurt3;
Organizations: 1Department of Clinical Biochemistry , Rigshospitalet, Copenhagen, Denmark
2Department of Cardiology, Rigshospitalet, Copenhagen, Denmark
3Department of Medicine, Institution of Public Health and Clinical Medicine, Umeå University, Skelleftå, Sweden
4Medicinsk Afdeling, OUH Svendborg Sygehus, Denmark
5Department of Medicine, Institute of Clinical Medicine, University of Oulu and Clinical Research Center, Oulu University Hospital, Oulu, Finland
6Manchester Academic Health Sciences Center, University Hospitals of South Manchester, Manchester, United Kingdom
7Center for Preventive medicine, Oslo University Hospital, Ullevål and University of Oslo, Oslo, Norway
8Department of Cardiology, Oslo University Hospital, Oslo, Norway
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 0.8 MB)
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Language: English
Published: Elsevier, 2019
Publish Date: 2020-09-07


In this study, we aimed to determine if pretreatment low-density lipoprotein (LDL) levels and aortic stenosis (AS) severity alter the efficacy of lipid-lowering therapy on reducing aortic valve replacement (AVR). We used 1,687 patients with asymptomatic mild-to-moderate AS, who were randomly assigned (1:1) to 40/10 mg simvastatin/ezetimibe combination versus. placebo in the simvastatin and ezetimibe in aortic stenosis (SEAS) trial. Pretreatment LDL levels (>4 mmol/L) and peak aortic jet velocity (3 m/s) were used to partition study participants into 4 groups, which were followed for a primary endpoint of AVR. Cox regression with tests for interaction was used to study the effect of randomized treatment in each subgroup. During a median follow-up of 4.3 years (IQR 4.2 to 4.7 years; total 7,396 patient-years of follow-up), 478 (28%) patients underwent AVR and 146 (9%) died. A significant risk dependency was detected between simvastatin/ezetimibe combination, LDL levels and mild versus moderate AS on rates of AVR (p = 0.01 for interaction). In stratified analyses, randomized treatment, therefore, reduced the rate of AVR in patients with LDL levels >4 mmol and mild AS at baseline (HR 0.4; 95% CI: 0.2 to 0.9). There was no detectable effect of randomized treatment on the need for AVR in the 3 other participants subgroups. We conclude, that in a secondary analysis from a prospective randomized clinical trial, treatment with simvastatin/ezetimibe combination reduced the need for AVR in a subset of patients with mild AS and high pretreatment LDL levels (Unique identifier on NCT00092677).

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Series: The American journal of cardiology
ISSN: 0002-9149
ISSN-E: 1879-1913
ISSN-L: 0002-9149
Volume: 124
Issue: 11
Pages: 1736 - 1740
DOI: 10.1016/j.amjcard.2019.08.037
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Copyright information: © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license