A Meta-Analysis of the Effect of PCSK9-Monoclonal Antibodies on Circulating Lipoprotein (a) Levels.

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.