Alshahrani Awad, Kholaif Naji, Al-Khnifsawi Mutaz, Zarif Hawazen, Mahzari Moeber
Department of Medicine, Ministry of the National Guard-Health Affairs, Riyadh, Saudi Arabia.
King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
Adv Ther. 2024 Feb;41(2):837-846. doi: 10.1007/s12325-023-02764-y. Epub 2024 Jan 2.
Achieving target low-density lipoprotein-cholesterol (LDL-C) levels remains challenging when treating homozygous familial hypercholesterolemia (HoFH). Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are prescribed in addition to statins and ezetimibe, but patients' response varies and depends on residual low-density lipoprotein receptor (LDLR) function.
A multicenter, retrospective observational analysis evaluated LDL-C target achievement in response to PCSK9i treatment in 28 patients with HoFH from the Middle East/North Africa region. Effect of genotype was investigated. Demographic and clinical information was retrospectively obtained from medical records. Patient response to PCSK9i treatment was assessed by calculating percentage changes in lipid levels from pre-PCSK9i treatment baseline to most recent follow-up visit where patients were recorded as receiving PCSK9i on top of standard of care lipid-lowering therapies (LLTs; i.e., statins/ezetimibe) and assessing European Atherosclerosis Society (EAS) target achievement up to January 31, 2022. Lowest LDL-C level while receiving PCSK9i was identified.
The cohort (n = 28) had a mean age (standard deviation; SD) of 22.8 (9.8) years (n = 28) and was 51% female (n = 27). Baseline LDL-C data were available in 24/28 (85.7%) patients (mean [SD] 14.0 [3.0] mmol/L). Median (interquartile range) duration of PCSK9i treatment was 12.0 months (4.0-19.1) months and mean (SD) % change in LDL-C after PCSK9i treatment was - 8.6% (12.1). LDL-C reduction from baseline was below 15% in 17/24 patients (70.8%). In the full cohort, mean (SD) minimum LDL-C during PCSK9i treatment was 11.9 (2.8; n = 28) mmol/L. No patient achieved EAS target LDL-C while receiving PCSK9i; genotype analysis suggested LDLR-null/null patients were most refractory to PCSK9i.
Response to PCSK9i was minimal in this cohort of patients with HoFH. No patients achieved EAS LDL-C targets, and most failed to reach the EAS-recommended 15% LDL-C reduction for PCSK9i therapy continuation. These results suggest additional LLTs are necessary to achieve LDL-C targets in HoFH.
在治疗纯合子家族性高胆固醇血症（HoFH）时，实现低密度脂蛋白胆固醇（LDL-C）目标水平仍然具有挑战性。除了他汀类药物和依折麦布外，还会使用前蛋白转化酶枯草溶菌素/kexin 9型抑制剂（PCSK9i），但患者的反应各不相同，且取决于残余低密度脂蛋白受体（LDLR）功能。
一项多中心回顾性观察分析评估了中东/北非地区28例HoFH患者接受PCSK9i治疗后LDL-C目标达成情况。研究了基因型的影响。从病历中回顾性获取人口统计学和临床信息。通过计算从PCSK9i治疗前基线到最近一次随访时血脂水平的百分比变化来评估患者对PCSK9i治疗的反应，在最近一次随访中，患者被记录为在标准护理降脂疗法（LLTs；即他汀类药物/依折麦布）基础上接受PCSK9i治疗，并评估截至2022年1月31日的欧洲动脉粥样硬化学会（EAS）目标达成情况。确定接受PCSK9i治疗期间的最低LDL-C水平。
该队列（n = 28）的平均年龄（标准差；SD）为22.8（9.8）岁（n = 28），女性占51%（n = 27）。24/28（85.7%）例患者有基线LDL-C数据（平均[SD] 14.0 [3.0] mmol/L）。PCSK9i治疗的中位（四分位间距）持续时间为12.0个月（4.0 - 19.1）个月，PCSK9i治疗后LDL-C的平均（SD）百分比变化为 - 8.6%（12.1）。17/24例患者（70.8%）的LDL-C较基线降低幅度低于15%。在整个队列中，接受PCSK9i治疗期间的平均（SD）最低LDL-C为11.9（2.8；n = 28）mmol/L。接受PCSK9i治疗期间，无患者达到EAS目标LDL-C；基因型分析表明，LDLR无功能/null患者对PCSK9i最耐药。
在该组HoFH患者中，对PCSK9i的反应很小。没有患者达到EAS的LDL-C目标，并且大多数患者未能达到EAS推荐的PCSK9i治疗持续进行所需的LDL-C降低15%的目标。这些结果表明，在HoFH患者中，需要额外的降脂疗法来实现LDL-C目标。
