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 vs. placebo in the simvastatin and ezetimibe in Aortic Stenosis (SEAS) trial. Pretreatment LDL levels (>4mmol/L) and peak aortic jet velocity (3m/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 4.2-4.7 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 vs. moderate AS on rates of AVR (p=0.01 for interaction). In stratified analyses, randomized treatment, therefore, reduced the rate of AVR among patients with LDL levels >4mmol and mild AS at baseline (HR 0.4; 95%CI: 0.2-0.9). 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 ).