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

C2 - 31586530

VL - 124

SP - 1736

EP - 1740

JO - American Journal of Cardiology

JF - American Journal of Cardiology

SN - 0002-9149

IS - 11

ER -