Effect of evolocumab on carotid plaque composition in asymptomatic carotid artery stenosis (EVOCAR-1) using magnetic resonance imaging

IF 3.6 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of clinical lipidology Pub Date : 2024-09-01 DOI:10.1016/j.jacl.2024.06.004

Ben Jones PhD , Neil Rane FRCR , Mary Finnegan PhD , Rebecca Quest PhD , Mariana Abdel-Malek MRCP , Luca Biasiolli PhD , Joseph Shalhoub PhD , Alun Davies FRCS , Naomi Loyse PhD , Paul Bassett MSc , Kausik K Ray FMedSci , Jaimini Cegla PhD

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引用次数: 0

Abstract

Background and Aims

To determine the effect of evolocumab treatment in patients with asymptomatic carotid artery stenosis ≥50% on carotid plaque morphology and composition, as determined by magnetic resonance imaging.

Methods

We conducted a double-blind randomized controlled trial in patients with asymptomatic carotid artery plaque with ≥50% stenosis and low-density lipoprotein-associated cholesterol (LDL-C) ≥1.8 mmol/L, despite standard lipid-lowering therapy, with 12 months of evolocumab or placebo injection every two weeks. The primary endpoint was the between group difference in the absolute change from baseline in carotid plaque lipid-rich necrotic core (LRNC), assessed by carotid magnetic resonance.

Results

Due to interrupted recruitment during the COVID-19 pandemic, 33 patients (36% female) were randomised, which was less than the target of 52. Mean age was 68.7 years (SD, 8.5) and baseline LDL-C 2.4 mmol/L (SD, 0.7). LDL-C was reduced with evolocumab to 0.8 mmol/L (SD, 0.5) vs 2.2 mmol/L (SD, 0.7) with placebo at 3 months (between group absolute difference -1.3 mmol/L [95% confidence interval [CI], -1.7 to -0.9], p < 0.001). Evolocumab treatment was associated with a favourable change in LRNC at 12 months of -16 mm³ (SD, 54) whereas the placebo group showed -4 mm³ (SD, 44). Between group differences did not show statistical significance with a placebo-adjusted LRNC change of -17 mm³ ([95% CI, -45 to 12], p = 0.25). Percentage carotid plaque LRNC also numerically reduced at 12 months, however this did not reach statistical significance (-2.4% vessel wall volume [95% CI, -5.7 to 0.9], p = 0.16).

Conclusion

Intensive LDL-C lowering with the addition of evolocumab to maximally tolerated lipid-lowering therapy did not lead to a statistically significant change in vulnerable plaque phenotype characteristics in patients with asymptomatic carotid artery stenosis, but the study was underpowered due to under-recruitment in the context of the COVID-19 pandemic.

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使用磁共振成像检查 Evolocumab 对无症状颈动脉狭窄患者颈动脉斑块构成的影响（EVOCAR-1）

背景和目的通过磁共振成像确定无症状颈动脉狭窄≥50%的患者接受 evolocumab 治疗对颈动脉斑块形态和组成的影响。方法我们对无症状颈动脉斑块狭窄≥50%且低密度脂蛋白相关胆固醇（LDL-C）≥1.8 mmol/L的患者进行了一项双盲随机对照试验，在接受标准降脂治疗后，每两周注射一次evolocumab或安慰剂，为期12个月。主要终点是通过颈动脉磁共振评估颈动脉斑块富脂坏死核心（LRNC）与基线相比的绝对变化的组间差异。结果由于在COVID-19大流行期间招募中断，33名患者（36%为女性）被随机分配，少于52名患者的目标。平均年龄为 68.7 岁（SD，8.5），基线 LDL-C 为 2.4 mmol/L（SD，0.7）。使用 Evolocumab 3 个月后，LDL-C 降至 0.8 mmol/L (SD, 0.5) vs 2.2 mmol/L (SD, 0.7) (组间绝对差异 -1.3 mmol/L [95% 置信区间 [CI], -1.7 to -0.9]，p < 0.001)。Evolocumab 治疗 12 个月后，LRNC 的变化幅度为-16 mm3（标度为 54），而安慰剂组为-4 mm3（标度为 44）。组间差异未显示出统计学意义，安慰剂调整后的LRNC变化为-17 mm3（[95% CI, -45 to 12], p = 0.25）。颈动脉斑块 LRNC 百分比在 12 个月时也有数字上的减少，但未达到统计学意义（血管壁体积-2.4% [95% CI, -5.7 to 0.9], p = 0.16）。结论在最大耐受性降脂治疗的基础上加用 evolocumab 强化降低 LDL-C 并未导致无症状颈动脉狭窄患者易损斑块表型特征发生统计学意义上的显著变化，但在 COVID-19 大流行的背景下，由于招募不足，该研究的作用力不足。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of clinical lipidology 医学-药学

CiteScore

7.00

自引率

6.80%

发文量

209

审稿时长

49 days

期刊介绍： Because the scope of clinical lipidology is broad, the topics addressed by the Journal are equally diverse. Typical articles explore lipidology as it is practiced in the treatment setting, recent developments in pharmacological research, reports of treatment and trials, case studies, the impact of lifestyle modification, and similar academic material of interest to the practitioner. While preference is given to material of immediate practical concern, the science that underpins lipidology is forwarded by expert contributors so that evidence-based approaches to reducing cardiovascular and coronary heart disease can be made immediately available to our readers. Sections of the Journal will address pioneering studies and the clinicians who conduct them, case studies, ethical standards and conduct, professional guidance such as ATP and NCEP, editorial commentary, letters from readers, National Lipid Association (NLA) news and upcoming event information, as well as abstracts from the NLA annual scientific sessions and the scientific forums held by its chapters, when appropriate.