Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts, USA.
Curr Opin Cardiol. 2019 Nov;34(6):721-727. doi: 10.1097/HCO.0000000000000678.
Residual risk for atherosclerotic cardiovascular disease (ASCVD) persists even among patients with optimal low-density lipoprotein cholesterol (LDL-C) levels. Randomized trials attempting to modulate other lipids beyond LDL-C have failed to demonstrate significant reductions in ischemic events.
Mounting evidence suggests that triglyceride elevation is an independent risk factor for ASCVD. Though trials of triglyceride-lowering therapy in the statin era have failed to provide protection from ASCVD events, subgroup analyses have revealed that those with the highest triglycerides at time of enrollment appeared to receive the greatest clinical benefit. REDUCE-IT was a trial that enrolled patients with high triglycerides despite having goal LDL-C levels on statin therapy. Treatment with icosapent ethyl, a highly purified omega-3 fatty acid (OM3FA), eicosapentaenoic acid ethyl ester, provided a 25% relative risk reduction for the primary composite cardiovascular endpoint (hazard ratio 0.75, 95% CI 0.68--0.83; P = 0.00000001), as well as a 30% relative risk reduction in total ischemic events (P = 0.00000000036).
Icosapent ethyl was rigorously shown to decrease residual risk for cardiovascular events, though the benefits seen were likely because of mechanisms beyond mere triglyceride lowering. Clinical application of icosapent ethyl in this cohort of patients with residual risk is urgently needed.
即使在低密度脂蛋白胆固醇(LDL-C)水平最佳的患者中,动脉粥样硬化性心血管疾病(ASCVD)的残余风险仍然存在。试图调节 LDL-C 以外的其他脂质的随机试验未能证明缺血事件有显著减少。
越来越多的证据表明,甘油三酯升高是 ASCVD 的一个独立危险因素。尽管他汀类药物时代的甘油三酯降低治疗试验未能提供 ASCVD 事件的保护,但亚组分析显示,在入组时甘油三酯最高的患者似乎获得了最大的临床获益。在 REDUCE-IT 试验中,尽管患者在他汀类药物治疗时 LDL-C 水平达标,但仍招募了甘油三酯水平高的患者。高纯度ω-3 脂肪酸(OM3FA)二十碳五烯酸乙酯(icosapent ethyl)的治疗使主要复合心血管终点的相对风险降低了 25%(风险比 0.75,95%CI 0.68-0.83;P=0.00000001),总缺血事件的相对风险降低了 30%(P=0.00000000036)。
icosapent ethyl 被严格证明可以降低心血管事件的残余风险,尽管所看到的益处可能是由于除了单纯降低甘油三酯以外的机制。迫切需要在这一残余风险患者群体中应用icosapent ethyl。