Lipid-lowering therapy with simvastatin and ezetimibe may reduce the need for aortic valve replacement (AVR) in patients with mild asymptomatic aortic stenosis (AS) and high low-density lipoprotein cholesterol (LDL-C) levels, according to study results published in the American Journal of Cardiology.

Lipid-lowering therapy is shown effective at lowering the risk for vascular atherosclerosis but may not effectively delay AS. Recently, secondary analysis from the simvastatin and ezetimibe in aortic stenosis trial showed that when combined, simvastatin and ezetimibe may slow the progression of peak aortic jet velocity in patients with mild AS and pretreatment LDL-C levels >4 mg/dL; however, it remains unknown whether LDL-C and AS severity interfere with the efficacy of this lipid-lowering therapy to delay AS. The researchers of the study sought to evaluate whether pretreatment LDL-C levels and the severity of AS can alter the efficacy of lipid-lowering therapy with simvastatin and ezetimibe in the reduction of AVR.

In this multicenter, randomized, double-blind, placebo-controlled study, researchers evaluated 1687 patients with asymptomatic mild to moderate AS. They randomly assigned each patient to a combination of 40 mg simvastatin and 10 mg ezetimibe or placebo and stratified study participants into 4 groups according to pretreatment LDL-C levels (>4 mg/dL) and peak aortic jet velocity (3 m/s). The primary endpoint was AVR. Researchers used Cox regression to examine the effect of lipid-lowering therapy vs placebo on a reduced need for AVR in each subgroup.


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The median follow-up was 4.3 (interquartile range, 4.2-4.7) years (total 7396 patient-years). During that time, 28% (n=478) of the patients had AVR and 9% (n=146) died. Researchers identified significant risk dependency among the lipid-lowering therapy, LDL-C, and mild vs moderate AS on AVR rates (Pinteraction =.01).

Results from stratified analyses showed that randomized treatment reduced AVR rate in a subgroup of patients with LDL-C >4 mg/dL and mild AS at baseline (hazard ratio 0.4; 95% CI, 0.2-0.9). Researchers did not detect a significant effect of lipid-lowering therapy vs placebo on AVR in the other 3 subgroups.

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The researchers of the study noted that the main limitation is that it did not measure lipoprotein(a) or experiment wise type 1 error rate.

The researchers of the study concluded that a combination lipid-lowering therapy of simvastatin and ezetimibe may reduce the need for AVR in patients with mild AS and LDL-C >4 mg/dL and is likely to benefit patients with early AS and high levels of LDL-C and/or lipoprotein(a).

Disclosure: This clinical trial was supported by Merck Sharp & Dohme Corp. Please see original reference for a full list of authors’ disclosures.

Reference

Greve AM, Bang CN, Boman K, et al. Relation of lipid-lowering therapy to need for aortic valve replacement in patients with asymptomatic mild to moderate aortic stenosis [published online September 7, 2019]. Am J Cardiol. doi:10.1016/j.amjcard.2019.08.037