Page Michael M, Ekinci Elif I, Burnett John R, Hooper Amanda J, Reid Nicola, Bishop Warrick, Florkowski Chris M, Scott Russell, O'Brien Richard C, Watts Gerald F
School of Medicine, University of Western Australia, Crawley, Western Australia, Australia.
Western Diagnostic Pathology, Myaree, Western Australia, Australia.
J Clin Apher. 2021 Feb;36(1):48-58. doi: 10.1002/jca.21839. Epub 2020 Sep 10.
Severe familial hypercholesterolaemia (FH) causes premature disability and death due to atherosclerotic cardiovascular disease and is refractory to standard lipid-lowering therapies. Lipoprotein apheresis (LA) has long been a standard of care for patients with severe FH, but is invasive, expensive and time-consuming for patients and their caregivers. Newer drug therapies, including the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, may reduce the need for LA.
We audited the records of 16 patients (eight homozygous, eight heterozygous) treated with LA in Australia and New Zealand, 14 of whom subsequently commenced PCSK9 inhibitor therapy. LA was performed by cascade filtration in all centres.
LDL-cholesterol was acutely lowered by 69 ± 7% in patients with homozygous FH and by 72 ± 9% in those with heterozygous FH, representing time-averaged reductions of 36 ± 12% and 34 ± 5%, respectively. LA was well-tolerated, and patients reported comparable quality of life to population and disease-related norms. After commencement of PCSK9 inhibitors, four of seven patients with homozygous FH had meaningful biochemical responses, with a reduction in the frequency of LA permitted in one patient and complete cessation in another. Four of seven patients with heterozygous FH were able to be managed without LA after commencing PCSK9 inhibitors.
While PCSK9 inhibitors have reduced the need for LA, some patients with severe FH continue to require LA, and will require it for the foreseeable future. However, emerging therapies, including angiopoetin-like 3 inhibitors, may further reduce the need for LA.
严重家族性高胆固醇血症（FH）会因动脉粥样硬化性心血管疾病导致过早残疾和死亡，并且对标准降脂疗法难治。脂蛋白分离术（LA）长期以来一直是严重FH患者的护理标准，但对患者及其护理人员来说具有侵入性、费用高且耗时。包括前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）抑制剂在内的新型药物疗法可能会减少对LA的需求。
我们审核了在澳大利亚和新西兰接受LA治疗的16例患者（8例纯合子、8例杂合子）的记录，其中14例随后开始接受PCSK9抑制剂治疗。所有中心均通过级联过滤进行LA。
纯合子FH患者的低密度脂蛋白胆固醇（LDL-C）急性降低了69±7%，杂合子FH患者降低了72±9%，分别代表平均时间降低了36±12%和34±5%。LA耐受性良好，患者报告的生活质量与总体和疾病相关规范相当。开始使用PCSK9抑制剂后，7例纯合子FH患者中有4例有显著的生化反应，1例患者LA频率降低，另1例完全停止。7例杂合子FH患者中有4例在开始使用PCSK9抑制剂后无需LA即可得到管理。
虽然PCSK9抑制剂减少了对LA的需求，但一些严重FH患者仍需要LA，并且在可预见的未来仍将需要。然而，包括血管生成素样3抑制剂在内的新兴疗法可能会进一步减少对LA的需求。
