Effects of Evolocumab on Carotid Intima-Media Thickness and Clinical Parameters in Patients Taking a Statin

Abstract

We determined the effects of evolocumab, a fully human monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9, on carotid intima-media thickness (IMT) and the factors associated with the change in carotid IMT in patients taking a statin. The change in carotid mean and maximum IMT before and after the initiation of evolocumab treatment was retrospectively analyzed in 229 statin-treated patients. The changes in clinical parameters, including serum lipid concentrations, were also evaluated. Evolocumab significantly reduced the increase in carotid mean and maximum IMT (0.09 ± 0.13 mm/year to −0.04 ± 0.16 mm/year, p < 0.001 and 0.17 ± 0.38 mm/year to 0.08 ± 0.47 mm/year, p = 0.02). Evolocumab reduced serum total cholesterol, low-density lipoprotein-cholesterol, triglyceride, and lipoprotein (a) concentrations (each p < 0.001), and increased serum high-density lipoprotein (HDL)-cholesterol concentrations (p = 0.01). Multiple linear regression analysis revealed that the change in HDL-cholesterol (standard coefficient (β) = −0.120, p = 0.04) and carotid mean IMT (β = −0.467, p < 0.001) were independently correlated with the change in carotid mean IMT during the administration of evolocumab, whereas the change in HDL-cholesterol (β = −0.208, p = 0.002) and log-triglyceride (β = −0.167, p = 0.01) independently correlated with the change in carotid maximum IMT. Evolocumab reduced the increase in carotid IMT in patients taking a statin. These results suggest that evolocumab is protective against carotid atherosclerosis in patients undergoing statin therapy.

Short-Term Treatment with Alirocumab, Flow-Dependent Dilatation of the Brachial Artery and Use of Magnetic Resonance Diffusion Tensor Imaging to Evaluate Vascular Structure: An Exploratory Pilot Study

“…Not surprisingly, carotid intima-media thickness also did not change in response to alirocumab due to the short treatment period, low sample size, and relatively low baseline intima-media thickness. Over a longer period of 12 months, a recent retrospective observational analysis suggested a reduction of carotid intima-media thickness by evolocumab in 229 patients with statin pre-treatment [ 28 ]. Moreover, carotid intima-media thickness was reduced by treatment with PCSK9-antibodies in addition to ongoing lipoprotein apheresis in only 14 heterozygous familial hypercholesterolemia patients.…”

Increased Carotid Intima-Media Thickness in Asymptomatic Individuals Is Associated with the PCSK9 (rs2149041) Gene Polymorphism in the Mexican Mestizo Population: Results of the GEA Cohort

“…High PCSK9 concentrations in plasma have been associated with vascular disorders [ 23 , 24 , 25 , 42 , 43 ]. Congruently, pharmacological inhibition of PCSK9 with evolucumab reduced the increase in CIMT along the time in patients treated with statin [ 44 ] and improved the vascular functionality as determined by carotid stiffness in patients with familial hypercholesterolemia [ 45 ]. These observations are in agreement with a rapid reduction of lipid content in carotid plaques achieved with PCSK9 inhibitor alirocumab [ 46 ].…”

Smoking and diabetes attenuate beneficial effects of PSCK9 inhibitors on arterial wall properties in patients with very high lipoprotein (a) levels

“…A study by Hirai et al. [ 36 ] reported that in patients with hypercholesterolaemia and high CV risk, 12 months of evolocumab reduced the increase in c-IMT in the statin-taking patients. The main disadvantage of their study, however, was that it was retrospective, and they had no control group.…”

“…Hirai et al. [ 36 ] reported that the change in triglyceride levels positively correlated with the change in maximum c-IMT during treatment with evolocumab in patients who were already taking statins. They suggested that the effects of evolocumab on c-IMT can be partially explained by the reduction in triglycerides.…”