Medizinische Klinik IV - Grosshadern, University Munich, Munich, Germany.
Curr Opin Lipidol. 2017 Dec;28(6):452-457. doi: 10.1097/MOL.0000000000000456.
Although lipid-lowering treatment with statins, ezetimibe, and PCSK9 inhibitors is a very successful strategy to prevent cardiovascular events, there is a need for further drug developments. Not all patients respond sufficiently to the available therapy (very high baseline values, intolerance). Furthermore, patients may be characterized by dyslipidemias not accessible to available drugs such as patients with homozygous familial hypercholesterolemia, chylomicronemia syndrome, or elevated lipoprotein(a). A number of drugs are being developed to close these gaps.
The focus is on new antibodies, antisense oligonucleotides, and small molecules that address different aspects of lipid metabolism. Many of these developments are promising as they decrease LDL-cholesterol and/or non-HDL-cholesterol and/or triglycerides and/or lipoprotein(a) in patients who so far cannot be treated sufficiently. These drugs are currently in different stages of development and being tested in clinical trials.
Some of the new lipid-lowering drugs have a very promising profile. However, eventually phase 3 and outcome trials will be required to prove the usefulness of these compounds in clinical practice. Furthermore, it is unlikely that they will change the primary lipidological approach (statin and ezetimibe) even if they prove successful.
尽管降脂治疗采用他汀类药物、依折麦布和 PCSK9 抑制剂是预防心血管事件的非常成功的策略,但仍需要进一步开发药物。并非所有患者对现有治疗均有充分反应(基线值非常高、不耐受)。此外,患者可能存在现有药物无法治疗的脂代谢异常,如家族性高胆固醇血症纯合子、乳糜微粒血症综合征或脂蛋白(a)升高的患者。目前正在开发许多药物来弥补这些空白。
重点是新的抗体、反义寡核苷酸和小分子,它们针对脂质代谢的不同方面。其中许多药物具有很大的开发前景,因为它们能降低 LDL-胆固醇和/或非 HDL-胆固醇和/或甘油三酯和/或脂蛋白(a),而这些患者迄今为止无法得到充分治疗。这些药物目前处于不同的开发阶段,并正在临床试验中进行测试。
一些新的降脂药物具有非常有前景的特征。然而,最终需要进行 3 期和结局试验来证明这些化合物在临床实践中的有效性。此外,即使它们被证明是成功的,它们也不太可能改变主要的脂质学方法(他汀类药物和依折麦布)。