Relation of lipid-lowering therapy to need for aortic valve replacement in patients with asymptomatic mild to moderate aortic stenosis
Greve, Anders M.; Bang, Casper N.; Boman, Kurt; Egstrup, Kenneth; Kesäniemi, Y. Antero; Ray, Simon; Pedersen, Terje R.; Wachtell, Kristian (2019-09-07)
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, https://doi.org/10.1016/j.amjcard.2019.08.037
© 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/.
https://creativecommons.org/licenses/by-nc-nd/4.0/
https://urn.fi/URN:NBN:fi-fe2019120545822
Tiivistelmä
Abstract
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 clinicaltrials.gov: NCT00092677).
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