Faculty of Health and Medical Sciences, Medical School, University of Western Australia, Perth, Western Australia, Australia.
Medpace Reference Laboratories, Cincinnati, Ohio, USA.
J Intern Med. 2022 Jun;291(6):870-876. doi: 10.1111/joim.13457. Epub 2022 Feb 9.
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.
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).
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).
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.
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。
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。
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）。
在 apo(a)浓度极高的他汀类药物治疗患者中，阿利西尤单抗通过增加清除率和降低 Lp(a)颗粒的产生来降低血浆 Lp(a)浓度，其作用机制为双重作用。
