Maidman Samuel D, Rosenson Robert S
Metabolism and Lipids Program, Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1030, New York, NY, 10029, USA.
BioDrugs. 2025 Jun 25. doi: 10.1007/s40259-025-00731-3.
Despite the modern era of effective and safe high-intensity statins and non-statin agents, a significant portion of patients are still unable to achieve guideline-recommended lipid goals for the prevention of atherosclerotic cardiovascular disease (ASCVD) events. Accordingly, novel strategies are needed to further mitigate residual risk for patients on the background of maximally tolerated lipid-lowering therapies. The past decade has seen an explosion of new agents leveraging ribonucleic acid (RNA)-based technology which reduce plasma lipoprotein levels. In this state-of-the-art review, we examine the ongoing clinical development of lipid-lowering RNA therapeutics. We discuss the efficacy and safety profiles of antisense oligonucleotides and small interfering RNA agents targeting low-density lipoprotein, lipoprotein(a), and triglyceride-rich lipoproteins. We also present challenges future clinical trials must answer to prove RNA therapeutics as a viable strategy for ASCVD prevention among patients with refractory hyperlipidemia.
尽管现代有高效且安全的高强度他汀类药物和非他汀类药物，但仍有很大一部分患者无法实现预防动脉粥样硬化性心血管疾病（ASCVD）事件的指南推荐血脂目标。因此，需要新的策略来进一步降低接受最大耐受降脂治疗的患者的残余风险。在过去十年中，利用基于核糖核酸（RNA）技术的新型药物大量涌现，这些药物可降低血浆脂蛋白水平。在这篇前沿综述中，我们研究了降脂RNA疗法的当前临床进展。我们讨论了针对低密度脂蛋白、脂蛋白（a）和富含甘油三酯的脂蛋白的反义寡核苷酸和小干扰RNA药物的疗效和安全性。我们还提出了未来临床试验必须回答的挑战，以证明RNA疗法是难治性高脂血症患者预防ASCVD的可行策略。
