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. (9th February 2022)

• Record Type: Journal Article
• Authors: Ying, Qidi; Chan, Dick C.; Pang, Jing; Marcovina, Santica M.; Barrett, Peter Hugh R.; Watts, Gerald F.
• Is Part Of: Journal of internal medicine. Volume 291:Number 6(2022)
• Page Start: 870
• Page End: 876
• Publication Date: 2022-02-09
• Subjects: alirocumab -- apolipoprotein(a) -- lipoprotein(a) -- PCSK9 -- stable isotope; Internal medicine -- Periodicals; Medicine -- Periodicals; 616
• DOI: 10.1111/joim.13457
• Languages: English
• ISSNs: 0954-6820

Abstract

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.