AUTHOR=Chen Ju , Zhao Faming , Lei Chengbin , Qi Tianjun , Xue Xin , Meng Yuan , Zhang Wenzhong , Zhang Hui , Wang Jian , Zhu Haijun , Cheng Cheng , Wang Qilei , Bi Chenglong , Song Beibei , Jin Chengwei , Niu Qiang , An Fengshuang , Li Bin , Huo Xiaoguang , Zhao Yunhe , Li Bo 

TITLE=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

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.999224

DOI=10.3389/fphar.2022.999224

ISSN=1663-9812

ABSTRACT=<p><bold>Background and Purpose:</bold> 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.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> 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% (<italic>p</italic> &lt; 0.001); total cholesterol (TC) decreased by approximately 34% (<italic>p</italic> &lt; 0.001); small dense low-density lipoprotein (sd-LDL) decreased by approximately 52% (<italic>p</italic> &lt; 0.001); and HDL-c increased by approximately 20% (<italic>p</italic> &lt; 0.001). B-mode ultrasonography showed that the length and thickness of the plaque and the hypoechoic area ratio were reduced (<italic>p</italic> &lt; 0.05). The plaque area, calcified area ratio, and lumen cross-sectional area changed little (<italic>p</italic> &gt; 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 (<italic>p</italic> &lt; 0.001). The enhanced intensity ratio of plaque/lumen [intensity ratio (P/L)] decreased from 0.37 ± 0.16 to 0.31 ± 0.14 (<italic>p</italic> = 0.009). The contrast agent area in plaque/area of plaque decreased from 19.20 ± 13.23 to 12.66 ± 9.59 (<italic>p</italic> = 0.003). The neovascularization score decreased from 2.64 ± 0.54 to 2.06 ± 0.86 (<italic>p</italic> &lt; 0.001). Subgroup analysis based on statin duration (&lt;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.</p><p><bold>Conclusion:</bold> This study found that evolocumab combined with moderate-intensity statins significantly improved the blood lipid profile and reduced carotid IPN.</p><p><bold>Clinical Trial Registration:</bold><ext-link ext-link-type="uri" xlink:href="https://www.clinicaltrials.gov/" xmlns:xlink="http://www.w3.org/1999/xlink">https://www.clinicaltrials.gov</ext-link>; identifier: NCT04423406.</p>