Division of Lipidology and Hatter Institute for Cardiovascular Research in Africa, Department of Medicine, University of Cape Town, Cape Town, South Africa.
National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan.
J Am Coll Cardiol. 2020 Jul 14;76(2):131-142. doi: 10.1016/j.jacc.2020.05.027.
Homozygous familial hypercholesterolemia (HoFH) is characterized by extremely elevated low-density lipoprotein-cholesterol (LDL-C) levels and early onset atherosclerotic cardiovascular disease despite treatment with conventional lipid-lowering treatment.
This study was designed to assess LDL-C reduction with the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab in adult patients with HoFH.
This randomized, double-blind, placebo-controlled, parallel-group, phase 3 study evaluated efficacy and safety of alirocumab 150 mg every 2 weeks. The primary endpoint was percent reduction from baseline in LDL-C versus placebo after 12 weeks of treatment.
Patients (N = 69) were randomized 2:1 to alirocumab or placebo. At baseline, background lipid-lowering treatment included 67 patients receiving statin (59 patients on high-intensity statin); 50 patients on ezetimibe; 10 patients on lomitapide; and 10 patients undergoing apheresis. Mean baseline LDL-C was 259.6 mg/dl in the placebo group and 295.0 mg/dl in the alirocumab group. At week 12, the least squares mean difference in LDL-C percent change from baseline was -35.6% (alirocumab [-26.9%] vs. placebo [8.6%]; p < 0.0001). Reductions (least squares mean difference) in other atherogenic lipids at week 12 were: apolipoprotein B, -29.8%; non-high-density lipoprotein cholesterol, -32.9%; total cholesterol, -26.5%; and lipoprotein(a), -28.4% (all p < 0.0001). No serious adverse events, permanent treatment discontinuations, or deaths due to treatment-emergent adverse events were reported during the double-blind treatment period.
In the largest randomized controlled interventional trial in HoFH patients to date, alirocumab resulted in significant and clinically meaningful reductions in LDL-C at week 12. Alirocumab was generally well tolerated, with a safety profile comparable to that of placebo. (Study in Participants With Homozygous Familial Hypercholesterolemia [HoFH] [ODYSSEY HoFH] NCT03156621.).
纯合子家族性高胆固醇血症（HoFH）的特征是低密度脂蛋白胆固醇（LDL-C）水平极高，且尽管接受了常规降脂治疗，仍会早期发生动脉粥样硬化性心血管疾病。
本研究旨在评估前蛋白转化酶枯草溶菌素/柯萨奇蛋白酶 9 抑制剂阿利西尤单抗在 HoFH 成年患者中的 LDL-C 降低效果。
这是一项随机、双盲、安慰剂对照、平行分组、3 期研究，评估了阿利西尤单抗 150mg 每 2 周 1 次的疗效和安全性。主要终点是治疗 12 周后与安慰剂相比，LDL-C 的百分比降低。
69 例患者按 2:1 随机分配至阿利西尤单抗或安慰剂组。基线时，背景降脂治疗包括 67 例接受他汀类药物（59 例接受高强度他汀类药物）；50 例接受依折麦布；10 例接受洛美他派；10 例接受血浆置换。安慰剂组的平均基线 LDL-C 为 259.6mg/dl，阿利西尤单抗组为 295.0mg/dl。在第 12 周时，LDL-C 百分比变化的最小二乘均数差值为-35.6%（阿利西尤单抗组为-26.9%，安慰剂组为 8.6%；p<0.0001）。第 12 周时其他致动脉粥样硬化脂质的降低（最小二乘均数差值）为：载脂蛋白 B，-29.8%；非高密度脂蛋白胆固醇，-32.9%；总胆固醇，-26.5%；脂蛋白（a），-28.4%（均 p<0.0001）。在双盲治疗期间，没有报告严重不良事件、永久性治疗中断或因治疗引起的不良事件而死亡。
在迄今为止针对 HoFH 患者的最大规模随机对照干预试验中，阿利西尤单抗在第 12 周时显著降低 LDL-C，且具有临床意义。阿利西尤单抗总体耐受性良好，安全性与安慰剂相当。（载脂蛋白 B 抑制剂在杂合子家族性高胆固醇血症（HoFH）患者中的研究[ODYSSEY HoFH]NCT03156621.）。
