Perelman School of Medicine, University of Pennsylvania, 34th and Civic Center Blvd., Philadelphia, PA 19104, USA.
US Clinical Development and Medical Affairs, Novartis Pharmaceuticals Corporation, One Health Plaza, Building 125, East Hanover, NJ 07936, USA.
J Clin Lipidol. 2022 Sep-Oct;16(5):574-582. doi: 10.1016/j.jacl.2022.06.009. Epub 2022 Jun 28.
Despite the development of new therapies to lower cardiovascular disease (CVD) risk in recent decades, the trend of reductions in CVD mortality has reversed. New therapies are essential for the prevention of first and recurrent CVD. The importance of lowering low-density lipoprotein cholesterol (LDL-C) in the management and prevention of atherosclerotic CVD (ASCVD) is widely reflected in clinical treatment guidelines; however, most patients with established ASCVD do not achieve guideline-recommended LDL-C targets. Common reasons include adherence challenges, public disinformation, statin tolerability issues, access barriers, and clinical inertia. Inclisiran is a novel small interfering ribonucleic acid (RNA) that lowers circulating LDL-C by ∼50% when added to maximally tolerated statins by mimicking the body's natural pathway of RNA interference to specifically prevent proprotein convertase subtilisin/kexin type 9 synthesis. The unique dosing regimen of inclisiran (initial, at 3 months, and then every 6 months) has the advantage of allowing for healthcare provider administration during recommended routine visits for patients with established ASCVD, which can circumvent adherence issues associated with currently available LDL-C-lowering therapies. Inclisiran has demonstrated favorable tolerability and safety for up to 3 years, and evidence from longer-term use is accumulating in ongoing studies. This review discusses the novel mechanism of action of inclisiran and its potential position in the clinical armamentarium.
尽管近几十年来开发了降低心血管疾病 (CVD) 风险的新疗法，但 CVD 死亡率下降的趋势已经逆转。新疗法对于预防首次和复发性 CVD 至关重要。降低低密度脂蛋白胆固醇 (LDL-C) 在动脉粥样硬化性 CVD (ASCVD) 管理和预防中的重要性广泛反映在临床治疗指南中；然而，大多数已确诊 ASCVD 的患者并未达到指南推荐的 LDL-C 目标。常见的原因包括依从性挑战、公众信息错误、他汀类药物耐受性问题、获取障碍和临床惯性。Inclisiran 是一种新型小干扰 RNA (RNA)，当与最大耐受剂量的他汀类药物联合使用时，可将循环 LDL-C 降低约 50%，通过模拟体内 RNA 干扰的天然途径，专门预防前蛋白转化酶枯草溶菌素/激肽释放酶 9 的合成。Inclisiran 的独特给药方案（初始剂量、第 3 个月和第 6 个月）的优点在于，它允许在建议的已确诊 ASCVD 患者常规就诊期间由医疗保健提供者进行管理，从而可以避免与目前可用的 LDL-C 降低疗法相关的依从性问题。Inclisiran 在长达 3 年的时间里表现出良好的耐受性和安全性，正在进行的研究正在积累更长时间使用的证据。这篇综述讨论了 inclisiran 的新型作用机制及其在临床武器库中的潜在地位。
