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

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Greve, Anders M ; Bang, Casper N ; Boman, Kurt ; Egstrup, Kenneth ; Kesäniemi, Y Antero ; Ray, Simon ; Pedersen, Terje R ; Wachtell, Kristian. / Relation of lipid-lowering therapy to need for aortic valve replacement in patients with asymptomatic mild to moderate aortic stenosis. In: The American journal of cardiology. 2019 ; Vol. 124, No. 11. pp. 1736-1740.

Bibtex

@article{107ec60b1e6e4836857e3e841347e431,
title = "Relation of lipid-lowering therapy to need for aortic valve replacement in patients with asymptomatic mild to moderate aortic stenosis",
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).",
author = "Greve, {Anders M} and Bang, {Casper N} and Kurt Boman and Kenneth Egstrup and Kes{\"a}niemi, {Y Antero} and Simon Ray and Pedersen, {Terje R} and Kristian Wachtell",
note = "Copyright {\circledC} 2019 Elsevier Inc. All rights reserved.",
year = "2019",
month = "12",
day = "1",
doi = "10.1016/j.amjcard.2019.08.037",
language = "English",
volume = "124",
pages = "1736--1740",
journal = "American Journal of Cardiology",
issn = "0002-9149",
publisher = "Excerpta Medica, Inc",
number = "11",

}

RIS

TY - JOUR

T1 - Relation of lipid-lowering therapy to need for aortic valve replacement in patients with asymptomatic mild to moderate aortic stenosis

AU - Greve, Anders M

AU - Bang, Casper N

AU - Boman, Kurt

AU - Egstrup, Kenneth

AU - Kesäniemi, Y Antero

AU - Ray, Simon

AU - Pedersen, Terje R

AU - Wachtell, Kristian

N1 - Copyright © 2019 Elsevier Inc. All rights reserved.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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).

AB - 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).

U2 - 10.1016/j.amjcard.2019.08.037

DO - 10.1016/j.amjcard.2019.08.037

M3 - Journal article

VL - 124

SP - 1736

EP - 1740

JO - American Journal of Cardiology

JF - American Journal of Cardiology

SN - 0002-9149

IS - 11

ER -

ID: 58441048