Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada, N6A 5K8.
Pharmacol Ther. 2012 Jul;135(1):31-43. doi: 10.1016/j.pharmthera.2012.03.005. Epub 2012 Mar 23.
Elevated low density lipoprotein cholesterol (LDL-C) levels have been associated with an increased risk for cardiovascular disease (CVD). Despite a 25-30% reduction in CVD risk with LDL-C reducing strategies, there is still a significant residual risk. Moreover, achieving target LDL-C values in individuals at high CVD risk is sometimes limited because of tolerability and/or efficacy. Thus, novel therapeutic agents are currently being developed to lower LDL-C levels further. This review will highlight some of these therapeutic agents including anti-sense oligonucleotides focused on apolipoprotein B, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, microsomal triglyceride transfer protein inhibitors, and thyromimetics. For each therapeutic class, an overview of the mechanism of action, pharmacokinetic data, and efficacy/safety evidence will be provided.
升高的低密度脂蛋白胆固醇（LDL-C）水平与心血管疾病（CVD）风险增加有关。尽管通过 LDL-C 降低策略降低 CVD 风险的幅度为 25-30%，但仍存在显著的残余风险。此外，由于耐受性和/或疗效，在高 CVD 风险个体中达到目标 LDL-C 值有时受到限制。因此，目前正在开发新型治疗药物以进一步降低 LDL-C 水平。本综述将重点介绍其中一些治疗药物，包括针对载脂蛋白 B 的反义寡核苷酸、前蛋白转化酶枯草溶菌素/凝血酶 9（PCSK9）抑制剂、微粒体甘油三酯转移蛋白抑制剂和甲状腺刺激素。对于每个治疗类别，将提供作用机制、药代动力学数据和疗效/安全性证据的概述。
