Department of Cardiology, 69106Onassis Cardiac Surgery Center, Athens, Greece.
Molecular Immunology Laboratory, 69106Onassis Cardiac Surgery Center, Athens, Greece.
J Cardiovasc Pharmacol Ther. 2021 Jan;26(1):51-58. doi: 10.1177/1074248420943079. Epub 2020 Jul 30.
AIM: We evaluated the lipid-lowering (LL) effect of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in patients with heterozygous familial hypercholesterolemia (HeFH) treated with LL-drugs and lipoprotein apheresis (LA). PATIENTS AND METHODS: The PCSK9i treatment (evolocumab 420 mg/4 weeks, alirocumab 150 mg/2 weeks, or alirocumab 75 mg/2 weeks: 9, 6, and 2 patients, respectively) was initiated in patients with HeFH (n = 17; aged 35-69 years, 10 men, previously treated with statins + ezetimibe ± colesevelam and LA sessions for 2-12 years). A lipid profile was obtained before and immediately after the LA session and before, 1 and 2 months after switching to PCSK9i treatment. The duration of PCSK9i therapy ranged from 3 to 18 months. RESULTS: Median total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) levels before LA were 268, 198, 46, and 126 mg/dL, respectively, and decreased (at the end of the LA session) to 117, 50, 40, and 51 mg/dL, respectively ( < .001 for TC and = .001 for all other comparisons). The median time-averaged LDL-C levels following LA were 155 (121, 176; median [25th, 75th percentile]) mg/dL. Median TC, LDL-C, and TG levels before PCSK9i therapy were 269, 190, and 127 mg/dL and decreased to 152, 100, and 95 mg/dL, respectively ( = .002, < .002, and < .03, respectively). Steady LDL-C levels with PCSK9i treatment were significantly lower compared with time-averaged LDL-C levels following LA (median value: 100 vs 155 mg/dL; = .008). With PCSK9i, from 13 patients with CHD, 6 (46.1%) patients achieved LDL-C <70 mg/dL, and 2 patients (15.4%) achieved LDL-C <100 mg/dL. Lipoprotein apheresis was discontinued in all patients except for 2 who continued once monthly. CONCLUSIONS: PCSK9i can reduce LDL-C more consistently over time compared with a transient decrease following LA in HeFH patients. PCSK9i therapy may reduce the frequency of LA. Larger trials are required to establish the clinical implications of PCSK9i in patients previously on LA.
目的：评估前蛋白转化酶枯草溶菌素/ kexin 9 型抑制剂（PCSK9i）在接受降脂药物和脂蛋白吸附（LA）治疗的杂合子家族性高胆固醇血症（HeFH）患者中的降脂（LL）效果。
患者和方法：在 HeFH 患者（n=17；年龄 35-69 岁，男性 10 例，之前接受他汀类药物+依折麦布±考来维仑治疗，LA 治疗 2-12 年）中开始使用 PCSK9i 治疗（依洛尤单抗 420mg/4 周、阿利西尤单抗 150mg/2 周或阿利西尤单抗 75mg/2 周：分别为 9、6 和 2 例）。在 LA 治疗前和 LA 治疗后立即以及在开始使用 PCSK9i 治疗前、1 个月和 2 个月时获得血脂谱。PCSK9i 治疗的持续时间为 3-18 个月。
结果：LA 前总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）和甘油三酯（TG）水平中位数分别为 268、198、46 和 126mg/dL，并分别下降（LA 治疗结束时）至 117、50、40 和 51mg/dL（TC 为 <.001，其他所有比较均为 =.001）。LA 后平均 LDL-C 水平中位数为 155（121，176；中位数[25 分位，75 分位]）mg/dL。PCSK9i 治疗前 TC、LDL-C 和 TG 水平中位数分别为 269、190 和 127mg/dL，分别降至 152、100 和 95mg/dL（ =.002，<.002 和 <.03，分别）。与 LA 后平均 LDL-C 水平相比，PCSK9i 治疗时 LDL-C 水平稳定显著降低（中位数：100 vs 155mg/dL； =.008）。在接受 PCSK9i 治疗的 13 例 CHD 患者中，6 例（46.1%）患者 LDL-C<70mg/dL，2 例（15.4%）患者 LDL-C<100mg/dL。除 2 例患者每月接受一次 LA 治疗外，所有患者均停止 LA 治疗。
结论：与 HeFH 患者 LA 后短暂下降相比，PCSK9i 可更持续地降低 LDL-C。PCSK9i 治疗可能会降低 LA 的频率。需要更大规模的试验来确定 PCSK9i 在之前接受 LA 治疗的患者中的临床意义。
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