McGill University Health Centre and Research Institute, Montréal, Québec, Canada.
McGill University, Montréal, Québec, Canada.
Curr Atheroscler Rep. 2024 Nov 22;27(1):7. doi: 10.1007/s11883-024-01252-0.
Elevated lipoprotein(a) (Lp[a]) is a genetically determined cardiovascular risk factor, causally linked to both atherosclerotic coronary artery disease and aortic stenosis. Elevated Lp(a) is widely prevalent, and several cardiovascular societies now recommend performing Lp(a) screening at least once in all adults. However, there are currently no approved drugs aimed specifically at lowering Lp(a). In this review, we describe several promising Lp(a)-lowering therapies in the drug development pipeline and outline what role these may have in future clinical practice.
Pelacarsen and olpasiran are two novel RNA-based injectable therapies which are being studied in ongoing phase 3 clinical trials, with the earliest of these to be concluded in 2025. These drugs act by degrading transcribed LPA mRNA, which would normally yield the apolipoprotein(a) constituent of Lp(a). Other candidate drugs, such as Lepodisiran, Zerlasiran, and Muvalaplin, are also in early-stage development. While there are presently no Lp(a)-lowering drugs available for routine clinical use, several promising candidates are currently under investigation. If these prove to be effective in randomized clinical trials, they will expand the cardiovascular care armamentarium and will allow clinicians to treat a presently unmitigated cardiovascular risk factor.
脂蛋白(a)（Lp[a]）升高是一种遗传性心血管危险因素，与动脉粥样硬化性冠状动脉疾病和主动脉瓣狭窄均有因果关系。Lp(a)升高的情况广泛存在，现在有几个心血管学会建议所有成年人至少进行一次 Lp(a)筛查。然而，目前尚无专门用于降低 Lp(a)的批准药物。在这篇综述中，我们描述了几种有前途的处于药物研发管道中的 Lp(a)降低疗法，并概述了这些疗法在未来临床实践中可能发挥的作用。
Pelacarsen 和 olpasiran 是两种新型的基于 RNA 的可注射疗法，目前正在进行的 3 期临床试验中进行研究，最早的试验将于 2025 年结束。这些药物通过降解转录的 LPA mRNA 起作用，而 LPA mRNA 通常会产生 Lp(a)中的载脂蛋白(a)成分。其他候选药物，如 Lepodisiran、Zerlasiran 和 Muvalaplin，也处于早期开发阶段。虽然目前尚无用于常规临床使用的 Lp(a)降低药物，但有几个有前途的候选药物正在研究中。如果这些药物在随机临床试验中被证明有效，它们将扩大心血管治疗的手段，并使临床医生能够治疗目前无法控制的心血管危险因素。
