Merćep Iveta, Strikić Dominik, Slišković Ana Marija, Reiner Željko
Division of Clinical Pharmacology, Department of Internal Medicine, University of Zagreb School of Medicine, 10000 Zagreb, Croatia.
Division of Clinical Pharmacology, Department of Internal Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia.
Pharmaceuticals (Basel). 2022 Jul 7;15(7):839. doi: 10.3390/ph15070839.
Dyslipidaemia is a well-known risk factor for the development of cardiovascular disease, a leading cause of morbidity and mortality in developed countries. As a consequence, the medical community has been dealing with this problem for decades, and traditional statin therapy remains the cornerstone therapeutic approach. However, clinical trials have observed remarkable results for a few agents effective in the treatment of elevated serum lipid levels. Ezetimibe showed good but limited results when used in combination with statins. Bempedoic acid has been thoroughly studied in multiple clinical trials, with a reduction in LDL cholesterol by approximately 15%. The first approved monoclonal antibodies for the treatment of dyslipidaemia, PCSK9 inhibitors, are currently used as second-line treatment for patients with unregulated lipid levels on statin or statin combination therapy. A new siRNA molecule, inclisiran, demonstrates great potential, particularly concerning compliance, as it is administered twice yearly and pelacarsen, an antisense oligonucleotide that targets lipoprotein(a) and lowers its levels. Volanesorsen is the first drug that was designed to target chylomicrons and lower triglyceride levels, and olezarsen, the next in-line chylomicron lowering agent, is currently being researched. The newest possibilities for the treatment of dyslipidaemia are ANGPTL3 inhibitors with evinacumab, already approved by the FDA, and EMA for the treatment of familial hypercholesterolemia. This article provides a short summary of new agents currently used or being developed for lipid lowering treatment.
血脂异常是心血管疾病发生的一个众所周知的危险因素，而心血管疾病是发达国家发病和死亡的主要原因。因此，医学界已经处理这个问题数十年了，传统的他汀类药物治疗仍然是基石性的治疗方法。然而，临床试验观察到一些药物在治疗血清脂质水平升高方面取得了显著效果。依折麦布与他汀类药物联合使用时显示出良好但有限的效果。贝派地酸已在多项临床试验中得到充分研究，可使低密度脂蛋白胆固醇降低约15%。首个获批用于治疗血脂异常的单克隆抗体，即前蛋白转化酶枯草溶菌素9（PCSK9）抑制剂，目前被用作他汀类药物或他汀类药物联合治疗后血脂水平未得到控制的患者的二线治疗药物。一种新的小干扰RNA（siRNA）分子inclisiran显示出巨大潜力，尤其是在依从性方面，因为它每年给药两次，还有靶向脂蛋白(a)并降低其水平的反义寡核苷酸pelacarsen。volanesorsen是首个旨在靶向乳糜微粒并降低甘油三酯水平的药物，而下一个降低乳糜微粒的药物olezarsen目前正在研究中。治疗血脂异常的最新可能性是血管生成素样蛋白3（ANGPTL3）抑制剂evinacumab，它已获得美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）批准用于治疗家族性高胆固醇血症。本文简要总结了目前用于或正在研发的降脂治疗新药。
