Thompson Gilbert R
Faculty of Medicine, Hammersmith Hospital Campus, Imperial College London, United Kingdom.
Curr Opin Lipidol. 2021 Dec 1;32(6):363-369. doi: 10.1097/MOL.0000000000000784.
Lipoprotein apheresis has been first line therapy for homozygous familial hypercholesterolaemia (FH) and other severe and refractory forms of dyslpidaemia for over 40 years but the recent advent of novel and potent LDL-lowering compounds necessitates a reappraisal of its role.
During the past decade a substantial amount of evidence has accumulated describing the effect of LDL-lowering with apheresis and conventional drug therapy upon the cardiovascular outcomes associated with homozygous and statin-refractory heterozygous FH. This has necessitated re-defining the target levels of LDL cholesterol needed to arrest progression of atherosclerosis in these situations. At the same time, evidence has accrued regarding the pathogenicity of raised levels of lipoprotein (a) and the promising role of apheresis in mitigating the adverse effects of the latter. The latest advance in treatment has been the introduction of three classes of novel and potent LDL-lowering compounds in the shape of inhibitors of Propertin convertase subtilisin kexin 9 (PCSK9), microsomal triglyceride transfer protein and angiopoietin-like 3.
These recent developments raise the question of whether these compounds will be used as adjuvants to bolster lipoprotein apheresis in FH homozygotes or whether they will render it obsolete, as is already occurring with PCSK9 inhibitors in FH heterozygotes.
四十多年来，脂蛋白分离术一直是纯合子家族性高胆固醇血症（FH）及其他严重难治性血脂异常的一线治疗方法，但新型强效低密度脂蛋白（LDL）降低化合物的出现使得有必要重新评估其作用。
在过去十年中，积累了大量证据，描述了通过分离术和传统药物治疗降低LDL对与纯合子及他汀类药物难治性杂合子FH相关的心血管结局的影响。这使得有必要重新定义在这些情况下阻止动脉粥样硬化进展所需的LDL胆固醇目标水平。与此同时，关于脂蛋白（a）水平升高的致病性以及分离术在减轻后者不良反应方面的潜在作用也有了相关证据。治疗方面的最新进展是引入了三类新型强效LDL降低化合物，即前蛋白转化酶枯草溶菌素9（PCSK9）抑制剂、微粒体甘油三酯转移蛋白抑制剂和血管生成素样3抑制剂。
这些最新进展引发了一个问题，即这些化合物会被用作辅助手段来加强FH纯合子中的脂蛋白分离术，还是会使其过时，就像在FH杂合子中PCSK9抑制剂已经出现的情况那样。
