Marrs Joel C, Anderson Sarah L
College of Pharmacy, Department of Clinical Pharmacy & Translational Science, The University of Tennessee Health Science Center, Nashville, TN, USA.
PeerView Institute for Medical Education, New York, NY, USA.
Drugs Context. 2024 Nov 28;13. doi: 10.7573/dic.2023-12-3. eCollection 2024.
Inclisiran is a synthetic small interfering RNA (siRNA) that inhibits the production of proprotein convertase subtilisin/kexin 9 (PCSK9) in hepatocytes by silencing the translation of PCSK9 mRNA. The result of this mechanism is a decrease in PCSK9 synthesis resulting in decreased degradation of the LDL receptor, leading to more LDL receptors being available to clear LDL cholesterol (LDL-C) from the circulation. Inclisiran received FDA approval in 2021 and EMA approval in 2020. The indication for inclisiran use is as an adjunct to diet and statin therapy for the treatment of adults with primary hyperlipidaemia, including those with heterozygous familial hypercholesterolaemia to reduce LDL-C. Inclisiran has demonstrated consistent LDL-C lowering in the range of 44-54%. Furthermore, inclisiran has been demonstrated to be a safe medication with indications of significant or serious adverse events when compared to placebo. Inclisiran is given as an initial subcutaneous dose followed by a repeat dose at 3 months and every 6 months thereafter. The 2022 American College of Cardiology Expert Consensus Decision Pathway includes inclisiran as an option for non-statin therapy in addition to maximally tolerated statin therapy in those at very high risk of atherosclerotic cardiovascular disease or those with LDL-C >190 mg/dL. The ORION-4, VICTORION-1 PREVENT and VICTORION-2 PREVENT trials are ongoing and designed to evaluate the ability of inclisiran to reduce major cardiovascular events in addition to LDL-C lowering but will not be completed for a few years.
inclisiran是一种合成的小干扰RNA（siRNA），它通过沉默前蛋白转化酶枯草杆菌蛋白酶/kexin 9（PCSK9）mRNA的翻译来抑制肝细胞中PCSK9的产生。这种机制的结果是PCSK9合成减少，导致低密度脂蛋白受体（LDL受体）降解减少，从而使更多的LDL受体可用于从循环中清除低密度脂蛋白胆固醇（LDL-C）。inclisiran于2021年获得美国食品药品监督管理局（FDA）批准，并于2020年获得欧洲药品管理局（EMA）批准。inclisiran的适用指征是作为饮食和他汀类药物治疗的辅助手段，用于治疗原发性高脂血症的成人，包括杂合子家族性高胆固醇血症患者，以降低LDL-C。inclisiran已证明能持续降低LDL-C，降低幅度在44%-54%之间。此外，与安慰剂相比，inclisiran已被证明是一种安全的药物，未出现显著或严重不良事件的迹象。inclisiran初始采用皮下注射给药，3个月后重复给药一次，此后每6个月给药一次。2022年美国心脏病学会专家共识决策路径将inclisiran列为非他汀类治疗的一种选择，适用于动脉粥样硬化性心血管疾病极高风险或LDL-C>190mg/dL的患者，作为最大耐受他汀类治疗之外的用药。ORION-4、VICTORION-1 PREVENT和VICTORION-2 PREVENT试验正在进行中，旨在评估inclisiran除降低LDL-C外减少主要心血管事件的能力，但几年内不会完成。
