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

BackgroundLipoprotein (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.MethodsPubMed, MEDLINE, Embase, ClinicalTrials.gov, Cochrane CENTRAL, Web of Scienceand 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.ResultsTwenty-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 150mg alirocumab biweekly (-24.6%, 95% CI -28.0 to -21.2) and 140mg 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.ConclusionsThe 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.