Maligłówka Mateusz, Dec Adrianna, Bułdak Łukasz, Okopień Bogusław
Department of Internal Medicine and Clinical Pharmacology, School of Medicine in Katowice, Medical University of Silesia in Katowice, 40-007 Katowice, Poland.
Pharmaceuticals (Basel). 2025 Jun 1;18(6):832. doi: 10.3390/ph18060832.
Hypercholesterolemia, accompanied by vascular inflammation, leads to the premature initiation and progression of atherosclerosis, and both are considered nowadays as well-established cardiovascular (CV) risk factors. For several years, proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is), drugs that reduce the degradation of the receptors for low-density lipoprotein cholesterol (LDLRs), have appeared to be a very efficient lipid-lowering therapy among patients with complications resulting from atherosclerotic cardiovascular disease (ASCVD). Previous studies showed that drugs used to fight hypercholesterolemia (predominantly statins) have significant pleiotropic effects, including anti-inflammatory effects. To date, data on the potential impact of PCSK9 inhibitors, especially inclisiran, on the course of inflammation is still lacking. Therefore, we conceived a study to evaluate the effects of inclisiran on the markers of subclinical inflammation (e.g., pentraxin 3 (PTX3), interleukin-18 (IL-18), and soluble cluster of differentiation 40 ligand (CD40L)) and compared their magnitude in patients at high CV risk, with and without established heterozygous familial hypercholesterolemia (HeFH). : A total of 24 patients at high cardiovascular risk, according to European Society of Cardiology (ESC) guidelines, with or without concomitant HeFH diagnosed using Dutch Lipid Clinic Network (DLCN) criteria, were enrolled in this study. Lipid concentrations and levels of subclinical inflammatory markers of atherosclerosis were measured at the beginning and after 3 months of therapy. : After three months of therapy with inclisiran, a statistically significant reduction included from 287.6 ± 94.15 to 215.2 ± 89.08 [mg/dL], = 0.022 and from 211.71 ± 52.72 to 147.64 ± 55.44 [mg/dL], < 0.001, and from 180.79 ± 73.33 to 114.65 ± 71.54 [mg/dL], = 0.031 and from 129.62 ± 46.75 to 63.39 ± 43.6 [mg/dL], < 0.001. Moreover significant drops were observed in concentrations of from 1336.33 ± 395.15 to 1121.75 ± 351.17 [pg/mL], = 0.013 and from 1610.76 ± 537.78 to 1376.92 ± 529.19 [pg/mL], = 0.017), and : from 11.89 (9.72-13.98) to 9.15 (8.62-10.06) [pg/mL], = 0.005 and : from 11.58 (10.87-16.97) to 9.65 (8.43-10.95) [pg/mL], = 0.003). There were no significant changes in the levels of sCD40L. : This study confirmed the ability of inclisiran to reduce LDL-c levels in patients at high cardiovascular risk just after one dose of the drug. Furthermore, it appeared that beyond its lipid-lowering effect, the drug may also affect some inflammatory processes involved in the initiation and progression of atherosclerosis.
高胆固醇血症伴有血管炎症，会导致动脉粥样硬化过早发生和进展，如今这两者都被视为公认的心血管（CV）危险因素。多年来，前蛋白转化酶枯草溶菌素/克新9型抑制剂（PCSK9is），即降低低密度脂蛋白胆固醇（LDLR）受体降解的药物，在患有动脉粥样硬化性心血管疾病（ASCVD）并发症的患者中似乎是一种非常有效的降脂疗法。先前的研究表明，用于对抗高胆固醇血症的药物（主要是他汀类药物）具有显著的多效性作用，包括抗炎作用。迄今为止，关于PCSK9抑制剂，尤其是inclisiran对炎症进程潜在影响的数据仍然缺乏。因此，我们构思了一项研究，以评估inclisiran对亚临床炎症标志物（如五聚体3（PTX3）、白细胞介素-18（IL-18）和可溶性分化簇40配体（CD40L））的影响，并比较其在有和没有确诊的杂合子家族性高胆固醇血症（HeFH）的高CV风险患者中的影响程度。：根据欧洲心脏病学会（ESC）指南，共有24名高心血管风险患者，无论是否伴有根据荷兰脂质诊所网络（DLCN）标准诊断的HeFH，被纳入本研究。在治疗开始时和治疗3个月后测量血脂浓度和动脉粥样硬化亚临床炎症标志物水平。：用inclisiran治疗三个月后，统计学上显著降低的指标包括：从287.6±94.15降至215.2±89.08[mg/dL]，P = 0.022；和从211.71±52.72降至147.64±55.44[mg/dL]，P < 0.001；和从180.79±73.33降至114.65±71.54[mg/dL]，P = 0.031；和从129.62±46.75降至63.39±43.6[mg/dL]，P < 0.001。此外，观察到显著下降的指标包括：从1336.33±395.15降至1121.75±351.17[pg/mL]，P = 0.013；和从1610.76±537.78降至1376.92±529.19[pg/mL]，P = 0.017）；以及：从11.89（9.72 - 13.98）降至9.15（8.62 - 10.06）[pg/mL]，P = 0.005；和：从11.58（10.87 - 16.97）降至9.65（8.43 - 10.95）[pg/mL]，P = 0.003）。sCD40L水平没有显著变化。：这项研究证实了inclisiran在给高心血管风险患者一剂药物后降低LDL-c水平的能力。此外，似乎除了其降脂作用外，该药物还可能影响一些参与动脉粥样硬化发生和进展的炎症过程。
