Effect of evolocumab on the progression of intraplaque neovascularization of the carotid based on contrast-enhanced ultrasonography (EPIC study): A prospective single-arm, open-label study

Abstract

Background and Purpose: The aim of this study was to explore the effect of half a year of evolocumab plus moderate-intensity statin treatment on carotid intraplaque neovascularization (IPN) and blood lipid levels. Methods: A total of 31 patients with 33 carotid plaques who received evolocumab plus statin treatment were included. Blood lipid levels, B-mode ultrasound and contrast-enhanced ultrasonography (CEUS) at baseline and after half a year of evolocumab plus statin therapy were collected. The area under the curve (AUC) reflected the total amount of acoustic developer entering the plaque or lumen within the 180 s measurement period. The enhanced intensity reflected the peak blood flow intensity during the monitoring period, and the contrast agent area reflected the area of vessels in the plaques. Results: Except for high-density lipoprotein cholesterol (HDL-c), all other lipid indices decreased. Compared with baseline, low-density lipoprotein cholesterol (LDL-c) decreased by approximately 57% (p < 0.001); total cholesterol (TC) decreased by approximately 34% (p < 0.001); small dense low-density lipoprotein (sd-LDL) decreased by approximately 52% (p < 0.001); and HDL-c increased by approximately 20% (p < 0.001). B-mode ultrasonography showed that the length and thickness of the plaque and the hypoechoic area ratio were reduced (p < 0.05). The plaque area, calcified area ratio, and lumen cross-sectional area changed little (p > 0.05). CEUS revealed that the area under the curve of plaque/lumen [AUC (P/L)] decreased from 0.27 ± 0.13 to 0.19 ± 0.11 (p < 0.001). The enhanced intensity ratio of plaque/lumen [intensity ratio (P/L)] decreased from 0.37 ± 0.16 to 0.31 ± 0.14 (p = 0.009). The contrast agent area in plaque/area of plaque decreased from 19.20 ± 13.23 to 12.66 ± 9.59 (p = 0.003). The neovascularization score decreased from 2.64 ± 0.54 to 2.06 ± 0.86 (p < 0.001). Subgroup analysis based on statin duration (<6 months and ≥6 months) showed that there was no significant difference in the AUC (P/L) or intensity ratio (P/L) at baseline or after half a year of evolocumab treatment. Conclusion: This study found that evolocumab combined with moderate-intensity statins significantly improved the blood lipid profile and reduced carotid IPN. Clinical Trial Registration: https://www.clinicaltrials.gov; identifier: NCT04423406.

Keywords: atherosclerotic cardiovascular disease; contrast-enhanced ultrasonography; evolocumab; intra-plaque neovascularization; proprotein convertase subtilisin-kexin type 9.

FIGURE 1

Our target goal for blood lipids was LDL-c<1.8 mmol/L; CEUS: contrast-enhanced ultrasound; ASCVD: arteriosclerotic cardiovascular disease; exclusion criteria: allergies to albumin or SonoVue; pregnancy; severe liver, kidney or thyroid dysfunction; severe arrhythmia, heart failure or hypertension; and diabetes patients with poor control of blood glucose who had used evolocumab before.

FIGURE 2

A representative patient who had a large plaque in the common carotid artery that was identified by B-mode ultrasound. The plaque morphology changed little between baseline and after half a year of therapy (A). CEUS revealed that the contrast agent area and microvessel density were obviously reduced after half a year of evolocumab plus statin treatment (B). The AUC (P/L) and the enhanced intensity (P/L) decreased significantly after half a year of treatment (E). Red arrows indicate vessels in the plaque, and blue arrows indicate calcified plaques. The changes in AUC (P/L) and enhanced intensity (P/L) of all included patients before and after half a year of treatment (C,D).