ABSTRACT

Treatment with icosapent ethyl 4 g/day, a highly purified and stable ethyl ester of eicosapentaenoic acid (EPA), demonstrated a significant reduction in atherosclerotic cardiovascular disease (ASCVD) events and death in REDUCE-IT. However, analyses of REDUCE-IT and meta-analyses have suggested that this clinical benefit is greater than can be achieved by triglyceride reduction alone. EPA therefore may have additional pleiotropic effects, including anti-inflammatory and anti-aggregatory mechanisms. EPA competes with arachidonic acid for cyclooxygenase and lipoxygenase, producing anti-inflammatory and anti-aggregatory metabolites rather than the more deleterious metabolites associated with arachidonic acid. Changing the EPA:arachidonic acid ratio may shift metabolic status from pro-inflammatory/pro-aggregatory to anti-inflammatory/anti-aggregatory. EPA also has antioxidant effects and increases synthesis of nitric oxide. Incorporation of EPA into phospholipid bilayers influences membrane structure and may help to prevent cardiac arrhythmias. Clinically, this may translate into improved vascular health, including regression of atherosclerotic plaque. Overall, EPA has a range of pleiotropic effects that contribute to a reduction in ASCVD.

摘要

在 REDUCE-IT 中，使用二十碳五烯酸 (EPA) 的高度纯化和稳定的乙酯 4 g/天 icosapent 乙酯治疗表明动脉粥样硬化性心血管疾病 (ASCVD) 事件和死亡显着减少。然而，REDUCE-IT 的分析和荟萃分析表明，这种临床益处比单独降低甘油三酯所能实现的要大。因此，EPA 可能具有额外的多效作用，包括抗炎和抗聚集机制。EPA 与花生四烯酸竞争环氧合酶和脂肪氧化酶，产生抗炎和抗聚集代谢物，而不是与花生四烯酸相关的更有害的代谢物。改变 EPA:花生四烯酸的比例可能会将代谢状态从促炎/促聚集转变为抗炎/抗聚集。EPA 还具有抗氧化作用并增加一氧化氮的合成。将 EPA 掺入磷脂双分子层会影响膜结构，并可能有助于预防心律失常。在临床上，这可能会转化为改善血管健康，包括动脉粥样硬化斑块的消退。总体而言，EPA 具有一系列有助于减少 ASCVD 的多效作用。