The use of statins and inhibitors of proprotein convertase subtilisin-kexin type 9 (PCSK 9) in patients with dyslipidemia

R. M. Lupachev, M. L. Maksimov
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Abstract

Scientific relevance. According to the WHO data, cardiovascular diseases rank first as the cause of human death. In 2022, 18,601,923 people died from cardiovascular diseases, which amounted to 33 % of the total mortality in the world. Malignant neoplasms rank second with 9,958,133 deaths, representing 17.6 % of total mortality. Among cardiovascular diseases, ischemic heart disease (IHD), the pathogenesis of which is associated with impaired cholesterol and lipoprotein metabolism, is leading. The use of statin drugs is recommended as a first-line lipid-lowering therapy. As an alternative to HMG-CoA reductase inhibitors (statins), proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9) were discovered in 2003, however, they are less popular due to insuf ficient data on these drugs and their costliness. Purpose of the work: to study the safety of using proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in patients with dyslipidemia and compare the advantages and disadvantages in relation to the ef fects of HMG-CoA reductase (statins). Discussion: The analysis of literature data has shown that the most frequent manifestations of intolerance to statins are muscle symptoms. The main mechanisms of statin-associated complications are mediated by inhibition of HMG-CoA reductase, as well as by the effect of drugs on cellular and subcellular processes, skeletal muscles and genetic features of patients. PCSK9 inhibitors have a fundamentally different mechanism of action — they bind and inactivate PCSK9, which leads to a decrease of low-density lipoprotein cholesterol in the blood level. A small number of undesirable reactions have been identified for drugs of this group, the most important of which is immunogenicity. However, even if patients have antibodies to PCSK9 inhibitor, the efficacy of the drug in reducing the level of low-density lipoproteins remains high.Conclusion. In medical studies, PCSK9 inhibitors have been shown to perform better compared to HMG-CoA reductase inhibitors; meanwhile, patients continue to use statins as lipid-lowering medications.
在血脂异常患者中使用他汀类药物和 9 型胰蛋白酶-枯草酶-kexin(PCSK 9)抑制剂
科学意义。根据世界卫生组织的数据,心血管疾病是导致人类死亡的首要原因。2022 年,18,601,923 人死于心血管疾病,占世界总死亡率的 33%。恶性肿瘤位居第二,死亡人数为9958133人,占总死亡率的17.6%。在心血管疾病中,缺血性心脏病(IHD)居首位,其发病机制与胆固醇和脂蛋白代谢障碍有关。建议使用他汀类药物作为一线降脂疗法。作为 HMG-CoA 还原酶抑制剂(他汀类药物)的替代药物,2003 年发现了蛋白转化酶枯草酶/kexin 9 型抑制剂(PCSK9),但由于这些药物的数据不足且价格昂贵,因此不太受欢迎。研究目的:研究在血脂异常患者中使用9型亚铁/kexin蛋白转换酶抑制剂(PCSK9)的安全性,并比较其与HMG-CoA还原酶(他汀类药物)作用的优缺点。讨论:文献数据分析显示,他汀类药物不耐受最常见的表现是肌肉症状。他汀类药物相关并发症的主要机制是抑制 HMG-CoA 还原酶,以及药物对细胞和亚细胞过程、骨骼肌和患者遗传特征的影响。PCSK9 抑制剂具有根本不同的作用机制--它们能与 PCSK9 结合并使其失活,从而降低血液中的低密度脂蛋白胆固醇水平。这类药物有少量不良反应,其中最重要的是免疫原性。不过,即使患者对 PCSK9 抑制剂产生抗体,该药物在降低低密度脂蛋白水平方面的疗效仍然很高。医学研究表明,与 HMG-CoA 还原酶抑制剂相比,PCSK9 抑制剂的疗效更好;与此同时,患者仍在使用他汀类药物作为降脂药物。
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