RESULTS
Characteristics of included trials
An initial search yielded 4687 articles, which were screened for relevance, leading to the selection of 348 articles. Following a rigorous selection process, 12 trials involving 392 HoFH patients were included in the meta-analysis [22 – 33] (Figure S1 ). Six RCTs used PCSK9i (n=152 patients) and in the other 6 RCTs the treatment with ANGTPL3i was applied (n=240 patients). The characteristics of included trials are presented in Table 1 . The mean age of the patients was 31.7 ± 13 and 48.4% were females. 55.2% of patients were with CVD disease when included in the trials. The prevalence of White patients was significantly higher compared to the Black, Asian or other races (75.4, 2.4, 8.49, 11%, p<0.01; respectively).
When comparing the summary mean differences (SMD) of patients treated with LLTs, patients age in the groups of PCSK9i and ANGPTL,3i trials were similar (30.8±14.8 vs. 33.3±12.2, p=0.07). However, the prevalence of female patients and the presence of CVD were significantly lower in patients treated with PCSK9i compared to those treated with ANGPTL3i (p<0.01 for both), (Table S3 ).
The mean baseline levels of TC [8.45 ± 3.2 mmol/L (326.7 ± 123.7 mg/dL) vs. 10.9 ± 3.9 mmol/L (421.5 ± 150.8 mg/dL); p < 0.001], LDL-C [7.17 ± 3.3 mmol/L (277.3 ± 127.6 mg/dL) vs. 9.64 ± 3.7 mmol/L (372.8 ± 143 mg/dL); p < 0.001], and Lp(a) [34.9 ± 12.9 mg/dL vs. 60.1 ± 36 mg/dL; p < 0.001] were significantly lower in the ANGPTL3i group compared to the PCSK9i group, whereas HDL-C, TG, Apo-B, and Apo-A levels did not differ significantly between the groups (p > 0.05 for all; Figure S2 ).