Department of Cardiology, Birmingham City Hospital.
Institute of Cardiovascular Sciences, University of Birmingham & Aston University, Birmingham.
Curr Opin Lipidol. 2024 Dec 1;35(6):281-289. doi: 10.1097/MOL.0000000000000954. Epub 2024 Sep 27.
Inclisiran is a small interfering RNA that blocks hepatocyte production of the PCSK9 (proprotein convertase subtilisin/kexin type 9) protein by specifically targeting PCKS9 mRNA in the cytoplasm. This results in reduced degradation of LDL receptors and thus lowers LDL cholesterol by around 50% in addition to other lipid-lowering therapies. beyond 6 years of therapy. This review covers the latest published data and outlines future studies currently in process.
To date, half a million doses have been given worldwide with no untoward adverse events thus far. The twice-yearly injections make it potentially very user-friendly. The large phase 3a trials saw no diminution of effect with time up to nearly 7 years. Very large phase 3b randomized controlled trials are underway and may produce significant reductions in major adverse cardiovascular events.
Inclisiran has been evaluated in numerous trials, primarily the ORION 9 26 , ORION 10 27 and ORION 11 28 studies, which demonstrated that in patients already on maximally tolerated statin therapy, biannual inclisiran injections reduced LDL cholesterol by up to 52% compared to placebo with a good safety profile. The only observed side effects were mild and transient at the injection site. As mentioned in the accompanying video, this adds to our armamentarium of lipid treatments.
Inclisiran 是一种小干扰 RNA，通过特异性靶向细胞质中的 PCKS9mRNA 来阻断肝细胞产生 PCSK9（蛋白水解酶原转化酶枯草杆菌蛋白酶/kexin 9 型）蛋白，从而减少 LDL 受体的降解，除其他降脂治疗外，还可降低 LDL 胆固醇约 50%。在 6 年以上的治疗中。这篇综述涵盖了最新发表的数据，并概述了目前正在进行的未来研究。
迄今为止，全世界已使用了 50 万剂，迄今为止尚无不良不良反应。每半年注射一次，可能非常便于使用。大型 3a 期试验表明，近 7 年的时间内，疗效没有随时间减弱。正在进行非常大型的 3b 期随机对照试验，可能会显著减少主要不良心血管事件。
Inclisiran 已在多项试验中进行了评估，主要是 ORION 9 26、ORION 10 27 和 ORION 11 28 研究，这些研究表明，在已经接受最大耐受剂量他汀类药物治疗的患者中，与安慰剂相比，每半年注射一次 inclisiran 可将 LDL 胆固醇降低多达 52%，安全性良好。唯一观察到的副作用是注射部位轻微且短暂。如随附视频中所述，这增加了我们的脂质治疗武器。
