PCSK9 inhibition
Evolocumab cuts Lp(a) by up to 29.5%, a pooled analysis of 4 phase 2 trials and 1359 patients (J Am Coll Cardiol 2014)
Original title: Reduction in lipoprotein(a) with PCSK9 monoclonal antibody evolocumab (AMG 145): a pooled analysis of more than 1,300 patients in 4 phase II trials
This pooled analysis of 4 phase 2 trials examined evolocumab (AMG 145) effect on Lp(a) in 1,359 patients, using a standardized isoform-independent assay. After 12 weeks, evolocumab produced significant, dose-related Lp(a) reductions versus control: 29.5% (95% CI 23.3%-35.7%) with 140 mg every 2 weeks and 24.5% (95% CI 20.4%-28.7%) with 420 mg every 4 weeks (both P<0.001), with no plateau of effect. Lp(a) reductions correlated with LDL cholesterol reductions (Spearman correlation 0.5134, P<0.001) and apolipoprotein B reductions (Spearman correlation 0.5203, P<0.001), and were greater in patients on background statin therapy, though not by age or sex. Mean percentage reduction was significantly greater in patients with baseline Lp(a) at or below 125 nmol/L, though absolute reduction was larger in those above 125 nmol/L. The findings show PCSK9 inhibition with evolocumab produces significant, dose-related Lp(a) reductions.
Original abstract
Objectives: The purpose of this study was assess the effect of evolocumab (AMG 145) on lipoprotein (Lp)(a) from a pooled analysis of 4 phase II trials.
Background: Lp(a), a low-density lipoprotein (LDL) particle linked to the plasminogen-like glycoprotein apolipoprotein(a), shows a consistent and independent positive association with cardiovascular disease risk in epidemiological studies. Current therapeutic options to reduce Lp(a) are limited.
Methods: A pooled analysis of data from 1,359 patients in 4 phase II trials assessed the effects of evolocumab, a fully human monoclonal antibody to PCSK9, on Lp(a), the relationship between Lp(a) and lowering of low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B, and the influence of background statin therapy. Lp(a) was measured using a standardized isoform-independent method.
Results: Evolocumab treatment for 12 weeks resulted in significant (p < 0.001) mean (95% confidence interval) dose-related reductions in Lp(a) compared to control: 29.5% (23.3% to 35.7%) and 24.5% (20.4% to 28.7%) with 140 mg and 420 mg, dosed every 2 and 4 weeks, respectively, with no plateau of effect. Lp(a) reductions were significantly correlated with percentages of reductions in LDL-C (Spearman correlation coefficient, 0.5134; p < 0.001) and apolipoprotein B (Spearman correlation coefficient, 0.5203; p < 0. 001). Mean percentage reductions did not differ based on age or sex but the trend was greater in those patients taking statins.
Conclusions: Inhibition of PCSK9 with evolocumab resulted in significant dose-related reductions in Lp(a). While the mean percentage of reduction was significantly greater in those patients with baseline Lp(a) of ≤125 nmol/l, the absolute reduction was substantially larger in those with levels >125 nmol/l.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.