Alirocumab and evolocumab cut Lp(a) by about 20% in familial hypercholesterolaemia, a meta-analysis of 11 RCTs and 2,408 patients (Endokrynol Pol 2023)

Original title: Impact of alirocumab/evolocumab on lipoprotein (a) concentrations in patients with familial hypercholesterolaemia: a systematic review and meta-analysis of randomized controlled trials

Endokrynol Pol · 1 January 2023 · 7

Dai H, Zhu Y, Chen Z, Yan R, Liu J, He Z, Zhang L, Zhang F, Yan S

This systematic review and meta-analysis of 11 randomised controlled trials (2,408 participants) through November 2022 examined the PCSK9 inhibitors alirocumab and evolocumab in patients with familial hypercholesterolaemia (FH). Both drugs significantly reduced Lp(a) versus placebo (weighted mean difference -20.10%, 95% CI -25.59% to -14.61%), with similar efficacy between evolocumab (-19.98%) and alirocumab (-20.54%). Treatment lasting 24 weeks or more produced greater Lp(a) reduction (-22.81%) than 12-week treatment (-17.61%), while heterozygous and homozygous FH patients showed similar responses (-20.07% and -20.04% respectively). All-cause adverse events did not differ significantly between drug and placebo groups (relative risk 1.05, 95% CI 0.98-1.12). The findings support alirocumab and evolocumab as effective Lp(a)-lowering options in FH, regardless of treatment duration or FH subtype.

Original abstract

Introduction: Familial hypercholesterolaemia (FH) is a common hereditary genetic disorder, characterized by elevated circulating low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] concentrations, leading to atherosclerotic cardiovascular disease (ASCVD). Two types of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors- alirocumab and evolocumab- are efficient drugs in the treatment of FH, which can effectively reduce Lp(a) levels.

Material And Methods: Embase, MEDLINE, and PubMed up to November 2022 were searched for randomized clinical trials (RCTs) evaluating the effect of alirocumab/evolocumab and placebo treatment on plasma Lp(a) levels in FH. Statistics were analysed by Review Manager (RevMan 5.3) and Stata 15.1.

Results: Eleven RCTs involved a total of 2408 participants. Alirocumab/evolocumab showed a significant efficacy in reducing Lp(a) [weighted mean difference (WMD): -20.10%, 95% confidence interval (CI): -25.59% to -14.61%] compared with placebo. In the drug type subgroup analyses, although the efficacy of evolocumab was slightly low (WMD: -19.98%, 95% CI: -25.23% to -14.73%), there was no difference with alirocumab (WMD: -20.54%, 95% CI: -30.07% to -11.02%). In the treatment duration subgroup analyses, the efficacy of the 12-week duration group (WMD: -17.61%, 95% CI: -23.84% to -11.38%) was lower than in the group of ≥ 24 weeks' duration (WMD: -22.81%, 95% CI: -31.56% to -14.07%). In the participants' characteristics subgroup analyses, the results showed that no differential effect of alirocumab/evolocumab therapy on plasma Lp(a) concentrations was observed (heterozygous FH [HeFH] WMD: -20.07%, 95% CI: -26.07% to -14.08%; homozygous FH [HoFH] WMD: -20.04%, 95% CI: -36.31% to -3.77%). Evaluation of all-cause adverse events (AEs) between alirocumab/evolocumab groups and placebo groups [relative risk (RR): 1.05, 95% CI: 0.98-1.12] implied no obvious difference between the 2 groups.

Conclusions: Anti-PCSK9 drugs (alirocumab and evolocumab) may be effective as therapy for reducing serum Lp(a) levels in FH, and no differences were observed in treatment durations, participant characteristics, and other aspects of the 2 types of PCSk9 inhibitors. However, further experimental studies and RCTs are warranted to clarify the mechanism of PSCK9 inhibitors to lowering Lp(a) concentrations in FH.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.