Teimur Kayani, Bachar Ahmad, Rachel Chang, Frank Qian, M. Sahinoz, Muhammad Rehan, Antonio Giaimo, Erica Spatz, Jiun-Ruey Hu
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引用次数: 0
摘要
尽管他汀类药物一直是降低动脉粥样硬化性心血管疾病(ASCVD)风险的药物降脂基石,但由于副作用或他汀类药物单药治疗的胆固醇降幅达不到目标水平,许多患者无法达到他汀类药物的目标剂量。近年来,除传统的小分子药物外,还出现了利用小干扰 RNA(siRNA)和反义寡核苷酸的疗法,降脂策略的范围不断扩大。在随机对照试验中显示出良好疗效的非他汀类疗法包括三磷酸腺苷柠檬酸裂解酶抑制剂、蛋白转换酶亚基酶/kexin 9(PCSK9)抑制抗体和 siRNA、ω-3 多不饱和脂肪酸、脂蛋白(a)基因抑制 siRNA 和 ASO,以及依折麦布等老式疗法。相比之下,胆固醇酯转移蛋白(CETP)抑制剂在随机试验中显示出的效果并不乐观。本综述旨在总结这些药物的证据,重点关注 III 期随机试验。
Beyond Statins: Novel Lipid-Lowering Agents for Reducing Risk of Atherosclerotic Cardiovascular Disease
Although statins have served as the cornerstone for pharmacological lowering of lipid levels in atherosclerotic cardiovascular disease (ASCVD) risk reduction, many patients are unable to achieve target doses of statin medication due to side effects or target levels of cholesterol reduction on statin monotherapy. The landscape of lipid-lowering strategies has expanded in recent years, with the emergence of therapies that make use of small interfering RNA (siRNA) and antisense oligonucleotides, in addition to traditional small-molecule agents. Non-statin therapies that have shown promising results in randomized controlled trials include adenosine triphosphate-citrate lyase inhibitors, proprotein convertase subtilisin/kexin 9 (PCSK9)-inhibiting antibodies and siRNA, omega-3 polyunsaturated fatty acids, and lipoprotein(a) gene-inhibiting siRNA and ASOs, in addition to older therapies such as ezetimibe. In contrast, cholesteryl ester transfer protein (CETP) inhibitors have shown less promising results in randomized trials. The purpose of this narrative review is to summarize the evidence for these medications, with a focus on phase III randomized trials.