Discussion
HeFH
CARDIOVASCULAR DISEASES
HeFH is significantly underdiagnosed and undertreated in many countries and the situation is even worse in China, posing a great threat to the patients and necessitating earlier and more effective pharmacological intervention on the basis of statins and ezetimibe [The average age of HeFH diagnosis in this study (49.6 years) was consistent with those reported for East Asian or Chinese patients with HeFH [In Chinese HeFH participants with higher baseline LDL-C levels and higher proportion of moderate-intensity statin use, the LDL-C-lowering effect of tafolecimab was generally similar to those of other approved PCSK9 antibodies observed in western population. In RUTHERFORD-2 trial, evolocumab 140 mg Q2W and 420 mg monthly achieved placebo-adjusted LDL-C reductions of 59.2% and 61.3% at week 12, respectively, in patients with HeFH [Another benefit of PCSK9 inhibition is reductions in lipoprotein(a) levels, a LDL-like lipoprotein associated with cardiovascular diseases. Cardiovascular outcome trials of alirocumab and evolocumab both suggested that lipoprotein(a) level lowering with PCSK9 inhibition was associated with a greater cardiovascular risk reduction beyond LDL-C lowering alone, indicating additional benefits from further reduction of lipoprotein(a). Current PCSK9 antibodies lowered lipoprotein(a) levels by approximately 25%, but were least effective in patients with high lipoprotein(a) level (>50 mg/dl), with a 14% reduction [Consistent with previously reported genetic profiles of HeFH, potential causative variants were most commonly detected in Seven compound heterozygotes with two In this study, with 84.5% of participants at very-high cardiovascular risk, tafolecimab demonstrated a favorable risk-benefit profile, with safety profile similar to those identified in previous studies and those of alirocumab and evolocumab [A major limitation of this study was the short treatment duration. Although improvements on lipid profiles were evident after 24-week treatment with tafolecimab, a future study is warranted to evaluate its long-term efficacy and cardiovascular benefits in patients with HeFH. Another limitation was that all participants were Chinese, limiting the generalizability of the results to patients of other races or ethnicities.