5-脂氧合酶抑制剂VIA-2291（阿曲留通）治疗对冠状动脉斑块进展的影响：一项CT血管造影系列研究
Effect of treatment with 5-lipoxygenase inhibitor VIA-2291 (atreleuton) on coronary plaque progression: a serial CT angiography study.
作者信息
Matsumoto Suguru, Ibrahim Reda, Grégoire Jean C, L'Allier Philippe L, Pressacco Josephine, Tardif Jean-Claude, Budoff Matthew J
机构信息
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California.
Montréal Heart Institute, Montréal, Canada.
出版信息
Clin Cardiol. 2017 Apr;40(4):210-215. doi: 10.1002/clc.22646. Epub 2016 Nov 24.
BACKGROUND
Inflammation has a key role in the process of atherosclerosis. Production of leukotrienes by 5-lipoxygenase has been linked to atherosclerotic plaques and cardiovascular events.
HYPOTHESIS
In this study, a selective 5-LO inhibitor will slow plaque progression using serial cardiac computed tomographic angiography (CCTA).
METHODS
Patients with recent acute coronary syndrome (ACS) were prospectively assigned to one of 3 VIA-2291 doses (25 mg, 50 mg, 100 mg) or placebo by oral administration. All groups underwent CCTA at baseline and at 6 months' follow-up. Plaque types such as low-attenuation plaque (LAP), fibro-fatty tissue (FF), fibro-calcified plaque (FC), and dense calcium plaque (DC) were measured based upon predefined density threshold, and changes from baseline CCTA were analyzed.
RESULTS
The final analysis included 54 patients (age, 56 ± 9 years; 85.1% male) with CCTA at baseline and 24 weeks. Evaluating on treatment VIA-2291 (all 3 doses, n = 37) demonstrated significant reductions in plaque progression compared with placebo (n = 17). VIA-2291 significantly reduced LAP (5.9 ± 20.7 mm vs -9.7 ± 33.3 mm ), FF (11.1 mm ± 13.3 mm vs -0.9 ± 2.7 mm ), and FC (-0.1 ± 6.22 mm vs -14.3 ± 6.2 mm ; all P < 0.05) and retarded the progression of DC (3.9 ± 3.2 mm vs 0.2 ± 0.4 mm ) compared with placebo.
CONCLUSIONS
VIA-2291 resulted in slowed plaque progression compared with placebo across different plaque subtypes in patients with recent ACS (http://ClinicalTrials.gov NCT00358826).
背景
炎症在动脉粥样硬化过程中起关键作用。5-脂氧合酶产生白三烯与动脉粥样硬化斑块及心血管事件有关。
假设
在本研究中，一种选择性5-LO抑制剂将通过连续心脏计算机断层血管造影（CCTA）减缓斑块进展。
方法
近期急性冠状动脉综合征（ACS）患者被前瞻性地随机分为口服3种VIA-2291剂量（25毫克、50毫克、100毫克）之一或安慰剂组。所有组在基线和6个月随访时均接受CCTA检查。根据预定义的密度阈值测量低衰减斑块（LAP）、纤维脂肪组织（FF）、纤维钙化斑块（FC）和致密钙斑块（DC）等斑块类型，并分析与基线CCTA相比的变化。
结果
最终分析纳入了54例患者（年龄56±9岁；85.1%为男性），他们在基线和24周时接受了CCTA检查。与安慰剂组（n = 17）相比，评估接受VIA-2291治疗（所有3个剂量组，n = 37）的患者显示斑块进展显著减少。与安慰剂相比，VIA-2291显著减少了LAP（5.9±20.7毫米对-9.7±33.3毫米）、FF（11.1毫米±13.3毫米对-0.9±2.7毫米）和FC（-0.1±6.22毫米对-14.3±6.2毫米；所有P < 0.05），并延缓了DC的进展（3.9±3.2毫米对0.2±0.4毫米）。
结论
与安慰剂相比，VIA-2291使近期ACS患者不同斑块亚型的斑块进展减缓（http://ClinicalTrials.gov NCT00358826）。
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