Department of Clinical Pharmacology, University Hospital Centre Zagreb, Croatia.
Department of Internal Medicine, University of Zagreb, School of Medicine, Croatia.
Cardiovasc Ther. 2022 Feb 10;2022:8129513. doi: 10.1155/2022/8129513. eCollection 2022.
As dyslipidemias remain one of the main risk factors for developing cardiovascular disease, the question of maintaining optimal lipid levels with pharmacotherapy remains a subject of interest worldwide. In contrast to conventional pharmacotherapy, human monoclonal antibodies directed against proprotein convertase subtilisin/kexin type 9 (PSCK9) and small interfering RNA- (siRNA-) based drug targeting PCSK9 represent a new strategy for managing lipid disorders and reducing cardiovascular risk. Inclisiran is a long-acting, synthetic siRNA that targets hepatic production of PCSK9 and consequently causes a reduction in LDL-C concentrations by approximately 50% compared to placebo. The structural modification of inclisiran has led to better stability and prolonged biological activity of the drug. The main advantage over conventional pharmacotherapy and anti-PCSK9 monoclonal antibodies is its favorable administration regimen (0-90-180 days), which should lead to much better compliance. Clinical trials conducted so far have confirmed the tolerability and efficacy of inclisiran in long-term PCSK9 and LDL-C level reductions. Moreover, a short-term follow-up on the safety of inclisiran showed a relatively good safety profile of the drug. However, it is still of great importance for ongoing and forthcoming clinical trials to be continued on a larger group of patients in order to assess long-term tolerability, efficacy, and safety of inclisiran.
由于血脂异常仍然是心血管疾病发展的主要危险因素之一,因此用药物治疗维持最佳血脂水平的问题仍然是全球关注的焦点。与传统的药物治疗相比,针对前蛋白转化酶枯草溶菌素/柯萨奇蛋白酶 9(PCSK9)的人源单克隆抗体和基于小干扰 RNA 的针对 PCSK9 的药物靶向治疗代表了管理血脂异常和降低心血管风险的一种新策略。依洛尤单抗是一种长效合成 siRNA,可靶向肝脏产生的 PCSK9,从而使 LDL-C 浓度降低约 50%,与安慰剂相比。依洛尤单抗的结构修饰导致药物稳定性更好,生物活性延长。与传统的药物治疗和抗 PCSK9 单克隆抗体相比,其主要优势在于其有利的给药方案(0-90-180 天),这应能提高更好的依从性。迄今为止进行的临床试验证实了依洛尤单抗在长期降低 PCSK9 和 LDL-C 水平方面的耐受性和疗效。此外,对依洛尤单抗安全性的短期随访显示,该药具有相对较好的安全性特征。然而,为了评估依洛尤单抗的长期耐受性、疗效和安全性,仍有必要在更大的患者群体中继续进行正在进行和即将进行的临床试验。