Hamasaki Masato, Kotani Kazuhiko
Division of Community and Family Medicine, Jichi Medical University, Shimotsuke-City, Tochigi 329-0498, Japan.
J Clin Med Res. 2025 Apr;17(4):181-186. doi: 10.14740/jocmr6196. Epub 2025 Apr 11.
Lipoprotein(a) (Lp(a)) is a type of lipoprotein consisting of low-density lipoprotein with apoprotein(a) (apo(a)) and is a risk factor for cardiovascular disease (CVD). Lowering Lp(a) levels may improve CVD outcomes, but this has been challenging owing to the unique structure and metabolic pathway of Lp(a). Recently, several new treatments using apo(a)-targeting drugs have been developed to reduce Lp(a) levels. Here, we briefly summarize the treatments, including earlier attempts at reducing Lp(a). Some lipid-lowering drugs can reduce Lp(a) levels in a non-targeted manner; while the effect of statins varies, niacin and proprotein convertase subtilisin/kexin type 9 inhibitors exhibit a reduction of over 20% in Lp(a) levels. Estrogen-related drugs and certain supplements can reduce Lp(a) levels, which may promote a deeper understanding of the modulation of Lp(a) levels. An apo(a) antisense oligonucleotide, small interfering RNAs, and a small molecule Lp(a)-formation inhibitor have recently been developed as promising drugs that specifically reduce Lp(a) levels by approximately 80%. The treatment strategies for Lp(a) are set to be updated, although we are awaiting clinical evidence on the reduction of CVD events by new treatments and the effective threshold for Lp(a) levels for the prevention of CVD.
脂蛋白(a)(Lp(a))是一种由低密度脂蛋白与载脂蛋白(a)(apo(a))组成的脂蛋白,是心血管疾病(CVD)的一个危险因素。降低Lp(a)水平可能会改善心血管疾病的预后,但由于Lp(a)独特的结构和代谢途径,这一直具有挑战性。最近,已经开发出几种使用靶向apo(a)的药物的新疗法来降低Lp(a)水平。在此,我们简要总结这些疗法,包括早期降低Lp(a)的尝试。一些降脂药物可以非靶向方式降低Lp(a)水平;虽然他汀类药物的效果各不相同,但烟酸和前蛋白转化酶枯草溶菌素/kexin 9型抑制剂可使Lp(a)水平降低超过20%。雌激素相关药物和某些补充剂可以降低Lp(a)水平,这可能有助于更深入地了解Lp(a)水平的调节。一种apo(a)反义寡核苷酸、小分子干扰RNA和一种小分子Lp(a)形成抑制剂最近已被开发为有前景的药物,可将Lp(a)水平特异性降低约80%。尽管我们正在等待关于新疗法降低心血管疾病事件以及预防心血管疾病的Lp(a)水平有效阈值的临床证据,但Lp(a)的治疗策略即将更新。