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.