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Effect of Evolocumab on Lipoprotein(a) and PCSK9 in Healthy Individuals with Elevated Lipoprotein(a) Level.

Olga I AfanasievaMarat V EzhovElena A KlesarevaOksana A RazovaUliana ChubykinaMane EgiazaryanEkaterina SherstyukMarina AfanasievaElena UtkinaSergei Pokrovsky
Published in: Journal of cardiovascular development and disease (2020)
Background and aims: The aim of this study was to investigate the influence of a single injection of Evolocumab on the dynamics of Lp(a), fractions of apoB100-containing lipoproteins, PCSK9, and their complexes in healthy individuals with elevated Lp(a) levels. Methods: This open-label, 4-week clinical study involved 10 statin-naive volunteers with Lp(a) >30 mg/dL, LDL-C < 4.9 mmol/L, and a moderate risk of cardiovascular events. The concentrations of Lp(a), lipids, PCSK9, circulating immune complexes (CIC), and plasma complexes of PCSK9 with apoB100-containing lipoproteins (Lp(a)-PCSK9 and LDL-PCSK9) were measured before and each week after Evolocumab (MABs) administration. Results: After a single dose injection of 140 mg of MABs, the median concentration of PCSK9 in serum increased from 496 to 3944 ng/mL; however, the entire pool of circulating PCSK9 remained bound with MABs for 2-3 weeks. LDL-C level decreased significantly from 3.36 mmol/L to 2.27 mmol/L during the first two weeks after the injection. Lp(a) concentrations demonstrated multidirectional changes in different patients with the maximal decrease on the second week. There were no positive correlations between the changes in levels of Lp(a), LDL-C, and TC. The change in the amount of circulating complex of PCSK9-Lp(a) was significantly less than of PCSK9-apoB100 (-5% and -47% after 1 week, respectively). Conclusions: A single administration of monoclonal antibodies against PCSK9 (Evolocumab) in healthy individuals with hyperlipoproteinemia(a) resulted in a decrease of Lp(a) of 14%, a 5% decrease in PCSK9-Lp(a), a 36% reduction of LDL-C, a 47% decrease in PCSK9-apoB100 and a tenfold increase in total serum PCSK9 concentration.
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