阿利西尤单抗抑制 PCSK9 可通过双重作用机制降低他汀类药物治疗的载脂蛋白(a)浓度极高的患者的血浆脂蛋白(a)浓度。

PCSK9 inhibition with alirocumab decreases plasma lipoprotein(a) concentration by a dual mechanism of action in statin-treated patients with very high apolipoprotein(a) concentration.

机构信息

Faculty of Health and Medical Sciences, Medical School, University of Western Australia, Perth, Western Australia, Australia.

Medpace Reference Laboratories, Cincinnati, Ohio, USA.

出版信息

J Intern Med. 2022 Jun;291(6):870-876. doi: 10.1111/joim.13457. Epub 2022 Feb 9.

DOI:10.1111/joim.13457

PMID:35112754

Abstract

BACKGROUND

Inhibition of proprotein convertase subtilisin/kexin type 9 with alirocumab decreases plasma lipoprotein(a) [Lp(a)] levels. The kinetic mechanism for lowering Lp(a) by alirocumab may differ according to pre-treatment apolipoprotein(a) [apo(a)] levels.

METHODS

The effect of 12-week alirocumab (150 mg subcutaneously fortnightly) on the kinetics of apo(a) was compared in statin-treated patients with high (n = 10) and very high Lp(a) concentrations (n = 11).

RESULTS

In patients with high apo(a) concentrations, alirocumab lowered plasma apo(a) pool size (-17%, p < 0.01) chiefly by increasing the fractional catabolic rate (FCR) of apo(a) (+27%, p < 0.001). By contrast in patients with very high apo(a) concentrations, alirocumab significantly lowered plasma apo(a) pool size (-32%, p < 0.001) by both increasing apo(a) FCR (+30%, p < 0.001) and lowering production rate (-11%, p < 0.05).

CONCLUSIONS

In statin-treated patients with very high apo(a) concentrations, alirocumab lowers plasma Lp(a) concentration by a dual mode of action that increases the clearance and decreases the production of Lp(a) particles.

摘要

背景

用阿利西尤单抗抑制脯氨酸蛋白酶原转化酶枯草溶菌素/柯萨奇蛋白酶 9 可降低血浆脂蛋白(a)[Lp(a)]水平。阿利西尤单抗降低 Lp(a)的动力学机制可能因治疗前载脂蛋白(a)[apo(a)]水平而异。

方法

比较了在他汀类药物治疗的高（n=10）和极高 Lp(a)浓度（n=11）的患者中，12 周阿利西尤单抗（150 mg 皮下每两周一次）对 apo(a)动力学的影响。

结果

在 apo(a)浓度高的患者中，阿利西尤单抗降低了血浆 apo(a)库大小（-17%，p<0.01），主要是通过增加 apo(a)的分解代谢率（FCR）（+27%，p<0.001）。相比之下，在 apo(a)浓度极高的患者中，阿利西尤单抗通过增加 apo(a)FCR（+30%，p<0.001）和降低产生率（-11%，p<0.05）显著降低了血浆 apo(a)库大小（-32%，p<0.001）。