Matsumoto Suguru, Ibrahim Reda, Grégoire Jean C, L'Allier Philippe L, Pressacco Josephine, Tardif Jean-Claude, Budoff Matthew J
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California.
Montréal Heart Institute, Montréal, Canada.
Clin Cardiol. 2017 Apr;40(4):210-215. doi: 10.1002/clc.22646. Epub 2016 Nov 24.
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.
In this study, a selective 5-LO inhibitor will slow plaque progression using serial cardiac computed tomographic angiography (CCTA).
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.
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.
VIA-2291 resulted in slowed plaque progression compared with placebo across different plaque subtypes in patients with recent ACS (http://ClinicalTrials.gov NCT00358826).
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。
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。
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。
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）。
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）。
