Improved endothelial function after short-term therapy with evolocumab.

Background: 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.

Objective: To assess whether treatment with PCSK9 inhibitors may improve endothelial function evaluated by brachial artery vasoreactivity test.

Methods: Brachial artery vasoreactivity test was performed in 14 consecutive patients with previous myocardial infarction before and after 2 months of therapy with evolocumab 140 mg 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.

Results: After 2 months of treatment with evolocumab, mean total cholesterol levels decreased from 245 ± 41 to 128 ± 30 mg/dL (P < .001, -48%), and LDL levels from 176 ± 43 to 71 ± 26 mg/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 ± 0.11 cm, P = .010; final values 0.36 ± 0.10 vs 0.34 ± 0.10 cm, P = .001), and velocity time integral (peak levels 96 ± 1 vs 85 ± 9 cm, P = .045).

Conclusions: Two months of treatment with evolocumab 140 mg may improve endothelial function in subjects with increased cardiovascular risk. The improvement in endothelial function is proportional to LDL reduction.