Improved endothelial function after short-term therapy with evolocumab

Abstract

The reduction of cholesterol levels with cholesterol-lowering therapy may improve endothelial function. Lipid-lowering therapy has been greatly enhanced by the introduction of proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies. Less is known of the effect of PCSK9 inhibitors on endothelial function of subjects with hypercholesterolemia. To assess whether treatment with PCSK9 inhibitors may improve endothelial function evaluated by brachial artery vasoreactivity test. Brachial artery vasoreactivity test was performed in 14 consecutive patients with previous myocardial infarction before and after 2months of therapy with evolocumab 140mg twice in a month. Mean brachial artery diameter, velocity time integral, flow-mediated dilation (FMD) and low-density lipoprotein (LDL) cholesterol levels were also evaluated. After 2months of treatment with evolocumab, mean total cholesterol levels decreased from 245±41 to 128±30mg/dL (P<.001, -48%), and LDL levels from 176±43 to 71±26mg/dL (P=.001, -59%); FMD conversely increased from 6.3±4.1% to 8.8±6.3% (P=.004,+40%). Improvement in FMD was proportional to reduction of LDL levels (r=0.69, P=.006). Therapy with evolocumab increased brachial artery diameter during vasoreactivity test (peak values 0.39±0.09 vs 0.36±0.11cm, P=.010; final values 0.36±0.10 vs 0.34±0.10cm, P=.001), and velocity time integral (peak levels 96±1 vs 85±9cm, P=.045). Two months of treatment with evolocumab 140mg may improve endothelial function in subjects with increased cardiovascular risk. The improvement in endothelial function is proportional to LDL reduction.