PCSK9 inhibition
PCSK9 monoclonal antibodies cut Lp(a) by 21.9% on average across 27 trials and 11,864 patients (Am J Cardiovasc Drugs 2019)
Original title: A Meta-Analysis of the Effect of PCSK9-Monoclonal Antibodies on Circulating Lipoprotein (a) Levels
This meta-analysis pooled 27 randomised clinical trials comprising 11,864 participants to evaluate the effect of PCSK9 monoclonal antibodies (PCSK9-mAbs) on circulating Lp(a) levels. PCSK9-mAbs significantly reduced Lp(a) overall (-21.9%, 95% CI -24.3 to -19.5), consistently across antibody type, treatment duration, participant characteristics, and baseline Lp(a) levels. The greatest reduction was achieved with 150 mg alirocumab biweekly (-24.6%, 95% CI -28.0 to -21.2) and 140 mg evolocumab monthly (-26.8%, 95% CI -31.6 to -21.9). Meta-regression showed greater LDL cholesterol declines during PCSK9-mAb treatment were associated with greater Lp(a) reductions. The findings confirm PCSK9-mAbs significantly reduce circulating Lp(a), though the authors call for long-term studies to confirm this effect.
Original abstract
Background: Lipoprotein (a) [Lp(a)] is an atherogenic lipoprotein. While no effective therapy for Lp(a) is currently available, recently, several pooled analyses with small sample sizes have suggested that proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9-mAbs) could reduce circulating Lp(a) levels. This meta-analysis was performed to comprehensively investigate the efficacy of PCSK9-mAbs with respect to serum Lp(a) concentrations.
Methods: PubMed, MEDLINE, Embase, ClinicalTrials.gov, Cochrane CENTRAL, Web of Science and recent conferences up to July 2018 were searched. Randomized clinical trials evaluating the effect of PCSK9-mAbs and control treatment on plasma Lp(a) concentrations were included. Mean differences and odds ratios with 95% confidence intervals (CIs) were used.
Results: Twenty-seven randomized clinical trials with a total of 11,864 participants were included. PCSK9-mAbs showed a significant efficacy in reducing Lp(a) (- 21.9%, 95% CI - 24.3 to - 19.5), irrespective of PCSK9-mAb types, treatment duration, participant characteristics, treatment methods, differences of control treatment, baseline Lp(a) levels, and test methods. The greatest reduction was achieved with 150 mg alirocumab biweekly (- 24.6%, 95% CI - 28.0 to - 21.2) and 140 mg evolocumab monthly (- 26.8%, 95% CI - 31.6 to - 21.9). Meta-regression analyses found that the more intense low-density lipoprotein cholesterol levels declined during PCSK9-mAb treatment, the greater the reduction in Lp(a) levels. Safety was in accordance with previous reports.
Conclusions: The results of this analysis suggested that PCSK9-mAbs could significantly reduce circulating Lp(a) levels. Long-term studies may be needed to confirm the effect of PCSK9-mAbs on Lp(a) in the future.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.