ANGPTL3 inhibitors demonstrated a greater reduction in mean LDL-C compared to PCSK9 inhibitors in patients with HoFH (-3.51 mmol/L vs. -1.81 mmol/L; p<0.001).
Meta-Analysis (n=392)
Do ANGPTL3 inhibitors reduce lipid levels more effectively than PCSK9 inhibitors in patients with homozygous familial hypercholesterolemia?
ANGPTL3 inhibitors are significantly more effective than PCSK9 inhibitors at reducing atherogenic lipid levels in patients with homozygous familial hypercholesterolemia.
p-value: p=<0.001
Abstract Background Homozygous familial hypercholesterolemia (HoFH) is a genetic disorder characterized by extremely high low-density lipoprotein cholesterol (LDL-C) levels, leading to early-onset atherosclerotic cardiovascular disease. The aim of this meta-analysis was to compare the efficacy of PCSK9 and ANGPTL3 inhibitors in patients with HoFH. Methods We systematically searched selected electronic databases until 30th November 2024. Main endpoint was the effect of lipid lowering therapy on lipid profile: total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and lipoproteins level levels. The secondary endpoint was adverse clinical effects. Results 12 trials (6 with PCSK9i and 6 with ANGPTL3i), involving a total of 392 patients with HoFH, were included in the meta-analysis. At a median follow-up of 12 months, the ANGPTL3i group demonstrated a greater reduction in mean TC –4.27 mmol/L (165.1 mg/dL) vs. –1.37 mmol/L (52.9 mg/dL); p for subgroup 0.001, LDL-C –3.51 mmol/L (135.7 mg/dL) vs. –1.81 mmol/L (69.9 mg/dL); p for subgroup 0.001, and TG –0.61 mmol/L (54.1 mg/dL) vs. –0.21 mmol/L (18.6 mg/dL); p for subgroup 0.001, but a smaller impact on HDL-C compared to those treated with PCSK9i. Likewise, Apo-B reduced more with ANGPTL3i compared to PCSK9i –0.81 g/L vs. –0.21 g/L; p 0.001, but Apo-A and Lipoprotein (a) remained comparable between the two groups (p 0.05 for both). The treatment-related adverse events and discontinuation rates were not different between groups (p 0.05 for both). Conclusions PCSK9 inhibitors have significantly lower efficacy in reducing lipid levels in HoFH patients compared to ANGPTL3 inhibitors, particularly in children. Further clinical trials are needed to compare their effectiveness across different functional variations of LDL-C receptors in HoFH patients.Figure 1.Summary mean change of lipid p Figure 2.Graphical abstract
Bytyci et al. (Sat,) conducted a meta-analysis in Homozygous familial hypercholesterolemia (HoFH) (n=392). ANGPTL3 inhibitors vs. PCSK9 inhibitors was evaluated on lipid profile: total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and lipoproteins level levels (p=<0.001). ANGPTL3 inhibitors demonstrated a greater reduction in mean LDL-C compared to PCSK9 inhibitors in patients with HoFH (-3.51 mmol/L vs. -1.81 mmol/L; p<0.001).
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