Victorian Heart Institute, Monash University, 631 Blackburn Road, Clayton, Melbourne, VIC, 3168, Australia.
Drugs. 2024 Jun;84(6):637-643. doi: 10.1007/s40265-024-02046-z. Epub 2024 Jun 8.
Increasing evidence has implicated lipoprotein(a) [Lp(a)] in the causality of atherosclerosis and calcific aortic stenosis. This has stimulated immense interest in developing novel approaches to integrating Lp(a) into the setting of cardiovascular prevention. Current guidelines advocate universal measurement of Lp(a) levels, with the potential to influence cardiovascular risk assessment and triage of higher-risk patients to use of more intensive preventive therapies. In parallel, considerable activity has been undertaken to develop novel therapeutics with the potential to achieve selective and substantial reductions in Lp(a) levels. Early studies of antisense oligonucleotides (e.g., mipomersen, pelacarsen), RNA interference (e.g., olpasiran, zerlasiran, lepodisiran) and small molecule inhibitors (e.g., muvalaplin) have demonstrated effective Lp(a) lowering and good tolerability. These agents are moving forward in clinical development, in order to determine whether Lp(a) lowering reduces cardiovascular risk. The results of these studies have the potential to transform our approach to the prevention of cardiovascular disease.
越来越多的证据表明脂蛋白(a)[Lp(a)]与动脉粥样硬化和钙化性主动脉瓣狭窄的病因有关。这激发了人们极大的兴趣,希望开发出将 Lp(a)纳入心血管预防的新方法。目前的指南主张普遍测量 Lp(a)水平,这有可能影响心血管风险评估,并将更高风险的患者分诊为使用更强化的预防治疗。与此同时,人们开展了大量工作来开发新的治疗方法,以期实现 Lp(a)水平的选择性和实质性降低。反义寡核苷酸(例如,mipomersen、pelacarsen)、RNA 干扰(例如,olpasiran、zerlasiran、lepodisiran)和小分子抑制剂(例如,muvalaplin)的早期研究已经证明了有效的 Lp(a)降低和良好的耐受性。这些药物正在临床开发中推进,以确定降低 Lp(a)是否能降低心血管风险。这些研究的结果有可能改变我们预防心血管疾病的方法。
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