Strength and limitations:
Our meta-analysis highlights the efficacy and safety of new lipid-lowering therapies (ANGPTL3i and PSCK9i) in patients with HoFH, one of the most challenging forms of dyslipidemia. Due to suboptimal treatment, HoFH patients remain carrying high risk for ASCVD, contributing to a significant burden of CV outcomes and premature mortality.
However, our meta-analysis has some limitations. Moderate heterogeneity was noted in some of the analyses, although we applied a random-effects model to reduce its impact. The trials included were single-arm, which precluded direct comparisons. Nonetheless, the sub-analysis, using mean differences with inverse variance, refuted any impact of the variations in sample size or age on the results. The available data were insufficient to draw definitive conclusions regarding the effectiveness and safety of the two new drug classes, particularly in the subgroups based on genetic mutations, primarily due to the limited number of trials. Future studies are crucial to assess LDL-C response in relation to genetic mutations, which should provide more precise and individualized treatment strategies for this patient population.
Conclusions: This meta-analysis showed that PCSK9 inhibitors have lower efficacy in reducing LDL-C levels in HoFH patients compared to ANGPTL3 inhibitors, particularly in children. Further clinical trials are needed to compare the effectiveness of the two treatments across different functional variations of LDL-C receptors in HoFH patients.
Conflict of interest: Maciej Banach: speakers bureau: Amgen, Daiichi Sankyo, KRKA, Polpharma, Mylan/Viatris, Novartis; all other authors do not declare any conflict of interest in relation to the results of this paper.
Maciej Banach
Funding: This research received no external funding.
Author contributions : I.B. and S.E.: Conceptualization, study design, methodology and project administration; I.B., S.B., D.G., M.S., E.D.: data analysis and writing the first draft of manuscript. M.B., M.Y.H., I.B., S.E.: Review manuscript. All authors have read and agreed to the published version of the manuscript.