Korneva V A, Kuznetsova T Yu
Petrozavodsk State University.
Kardiologiia. 2025 Jul 7;65(6):74-80. doi: 10.18087/cardio.2025.6.n2950.
It is of interest to study a possibility of switching a patient from one class of lipid-lowering drugs, inhibitors of proprotein convertase subtilisin/kexin type 9 (iPCSK9), to another (inclisiran), when the patient has already reached the target level of low-density lipoprotein cholesterol (LDL-C). From a pharmacological point of view, iPCSK9 and small interfering RNA (siRNA) drugs are completely different classes of drugs, although they affect the same target reducing the degradation of low-density lipoprotein (LDL) receptors. Alirocumab and evolocumab directly block circulating PCSK9 in the blood, which leads to an immediate decrease in the blood concentration of LDL-C clinically manifested already on the 1st day after injection. However, inclisiran has a different mechanism of action; it binds to PCSK9 matrix RNA, and shows a clinical effect of reduced the blood level of LDL-C later. In this article, we described several clinical cases of such switches and analyzed the risks for the patient associated with these situations. When changing an iPCSK9 targeted drug in clinical practice, we observed a change in the blood lipid composition, which affected the achievement of the LDL-C goal by the patient. Alirocumab demonstrated the greatest reduction in LDL-C (-56.5% compared to baseline in the first clinical case and -53% in the second), while the inclisiran treatment resulted in 31.4% and 36.2% decreases in LDL-C from baseline, respectively. These cases support a practical approach to changes in therapy; there is no need to change the PCSK9-targeted drug if the patient has achieved the LDL-C goal. However, if a change in therapy is necessary for a number of independent reasons, it is important to monitor blood levels of LDL-C on a regular basis due to the different lipid-lowering efficacy of the drugs. These cases illustrate the importance of a balanced approach to changes in the therapy for dyslipidemia when the patient has achieved the goal and is tolerating the treatment well.
当患者已经达到低密度脂蛋白胆固醇（LDL-C）目标水平时，研究将患者从一类降脂药物，即前蛋白转化酶枯草溶菌素/kexin 9型抑制剂（iPCSK9）转换为另一类药物（inclisiran）的可能性是很有意义的。从药理学角度来看，iPCSK9和小干扰RNA（siRNA）药物是完全不同类别的药物，尽管它们作用于相同靶点以减少低密度脂蛋白（LDL）受体的降解。阿利西尤单抗和依洛尤单抗直接阻断血液中循环的PCSK9，这导致注射后第1天临床上就已表现出LDL-C血液浓度立即下降。然而，inclisiran具有不同的作用机制；它与PCSK9基质RNA结合，并在之后显示出降低LDL-C血液水平的临床效果。在本文中，我们描述了几例此类转换的临床病例，并分析了与这些情况相关的患者风险。在临床实践中更换iPCSK9靶向药物时，我们观察到血脂成分发生变化，这影响了患者实现LDL-C目标。阿利西尤单抗使LDL-C降低幅度最大（在第一个临床病例中与基线相比降低了56.5%，在第二个病例中降低了53%），而inclisiran治疗分别使LDL-C较基线水平降低了31.4%和36.2%。这些病例支持了一种治疗方案改变的实用方法；如果患者已实现LDL-C目标，则无需更换PCSK9靶向药物。然而，如果由于一些独立原因需要改变治疗方案，由于药物的降脂效果不同，定期监测LDL-C血液水平很重要。这些病例说明了在患者已实现目标且对治疗耐受性良好的情况下，对血脂异常治疗方案改变采取平衡方法的重要性。
