Zwol Willemien van, Rimbert Antoine, Kuivenhoven Jan Albert
Department of Pediatrics, Section Molecular Genetics, University of Groningen, University Medical Centre Groningen, 9713 Groningen, The Netherlands.
J Clin Med. 2019 Jul 23;8(7):1085. doi: 10.3390/jcm8071085.
The recent introduction of inhibitors of proprotein convertase subtilisin/kexin 9 to lower low-density lipoprotein (LDL) cholesterol on top of statins or as monotherapy is rapidly changing the landscape of treatment of atherosclerotic cardiovascular disease (ASCVD). However, existing lipid-lowering drugs have little impact on lipoprotein(a) (Lp(a)) or plasma triglycerides, two other risk factors for ASCVD. This review summarizes the evidence and the rationale to target Lp(a) and triglycerides and provides an overview of currently tested strategies to lower Lp(a), apolipoprotein C-III and angiopoietin-like protein 3. In addition, it summarizes new findings on the use of omega-3 fatty acids (OM3FA) to fight ASCVD. With the exception of OM3FA supplementation, the promise of the experimental drugs discussed here depends on the long-term safety and efficacy of monoclonal antibodies and/or antisense oligonucleotides Clinical outcome trials will ultimately prove whether these new therapeutic modalities will reduce ASCVD risk.
近期,在他汀类药物基础上或作为单一疗法使用前蛋白转化酶枯草溶菌素/kexin 9抑制剂来降低低密度脂蛋白(LDL)胆固醇,这正在迅速改变动脉粥样硬化性心血管疾病(ASCVD)的治疗格局。然而,现有的降脂药物对脂蛋白(a)(Lp(a))或血浆甘油三酯影响甚微,而后两者是ASCVD的另外两个风险因素。本综述总结了针对Lp(a)和甘油三酯的证据及理论依据,并概述了目前用于降低Lp(a)、载脂蛋白C-III和血管生成素样蛋白3的测试策略。此外,还总结了使用ω-3脂肪酸(OM3FA)对抗ASCVD的新发现。除了补充OM3FA外,本文讨论的实验性药物的前景取决于单克隆抗体和/或反义寡核苷酸的长期安全性和有效性。临床结局试验最终将证明这些新的治疗方式是否会降低ASCVD风险。