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英克西兰的疗效、益处及安全性。

Efficacy, benefit and safety of inclisiran.

作者信息

López-Miranda José

机构信息

Unidad de Lípidos y Arteriosclerosis, Departamento de Medicina Interna, Hospital Universitario Reina Sofía, Universidad de Córdoba, IMIBIC, CIBEROBN, Córdoba, España.

出版信息

Clin Investig Arterioscler. 2024 Dec;36 Suppl 1:S24-S30. doi: 10.1016/j.arteri.2024.07.003.

Abstract

Hypercholesterolemia is a causal factor of atherosclerotic cardiovascular disease (ASCVD), which is one of the main causes of morbidity and mortality in Spain. The reduction of LDL cholesterol (LDL-C) decreases the risk of ASCVD and adverse cardiovascular events. Targeted therapy for the proprotein convertase subtilisin/kexin type 9 (PCSK-9) has emerged as a novel tool for the treatment of hyperlipidemia. Inclisiran is a small double-stranded small interfering RNA that acts by blocking PCSK-9 transcription in hepatocytes, leading to a marked and sustained reduction in circulating LDL-C levels. In contrast to other lipid-lowering therapies such as statins, ezetimibe and monoclonal antibodies PCSK-9 inhibitors, Inclisiran proposes an infrequent dosing regimen of twice times a year. Its prolonged effect represents an advantage over non-compliance of the treatment, which is one of the main reasons why LDL-C goals are not achieved with standard therapy. This review aims to present and discuss current scientific data regarding the efficacy, tolerability and safety of Inclisiran in the treatment of hypercholesterolemia. Inclisiran has been shown to provide significant long-term reductions in LDL-C levels associated with notable decreases in levels of PCSK9 and other atherogenic lipoproteins with a highly favourable side effect profile similar to placebo. The convenience of a twice-yearly dosing regimen promotes adherence to therapy and facilitates achievement of LDL-C goals. Results from ongoing trials designed to determine its effect on cardiovascular events are expected to provide further information about the cardiovascular benefit of inclisiran in patients with ACVD and in patients at high cardiovascular risk.

摘要

高胆固醇血症是动脉粥样硬化性心血管疾病(ASCVD)的一个致病因素,而ASCVD是西班牙发病和死亡的主要原因之一。降低低密度脂蛋白胆固醇(LDL-C)可降低ASCVD风险和不良心血管事件的发生风险。靶向治疗前蛋白转化酶枯草溶菌素/kexin 9型(PCSK-9)已成为治疗高脂血症的一种新工具。英克西兰是一种小的双链小干扰RNA,其作用机制是阻断肝细胞中PCSK-9的转录,从而导致循环LDL-C水平显著且持续降低。与其他降脂疗法如他汀类药物、依折麦布和PCSK-9抑制剂单克隆抗体不同,英克西兰采用每年两次的不频繁给药方案。其长效作用相对于治疗依从性不佳具有优势,而治疗依从性不佳是标准治疗无法实现LDL-C目标的主要原因之一。本综述旨在介绍和讨论关于英克西兰治疗高胆固醇血症的疗效、耐受性和安全性的当前科学数据。已证明英克西兰可显著长期降低LDL-C水平,同时PCSK9和其他致动脉粥样硬化脂蛋白水平显著降低,且副作用谱与安慰剂相似,非常有利。每年两次给药方案的便利性促进了治疗依从性,并有助于实现LDL-C目标。旨在确定其对心血管事件影响的正在进行的试验结果,有望提供关于英克西兰对ACVD患者和心血管高风险患者心血管益处的更多信息。

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