Procedures
Eligible participants were randomized in a 2:2:1:1 ratio to receive subcutaneous tafolecimab 150 mg Q2W, tafolecimab 450 mg Q4W, placebo Q2W or placebo Q4W, respectively, in the 12-week double-blind treatment period. Randomization was implemented by an interactive web response system and was stratified by LDL-C levels at screening (≥ or < 4.8 mmol/L), by baseline ezetimibe use (yes/no) and by prior use of PCSK9 inhibitors (yes/no). The participants, investigators and study site personnel involved in treating and assessing participants were masked to treatment allocations.After the 12-week double-blind treatment period, participants receiving tafolecimab continued to receive open-label tafolecimab with the previous regimens while participants receiving placebo Q2W or Q4W crossed over to receive open-label tafolecimab 150 mg Q2W or 450 mg Q4W, respectively, for 12 weeks, followed by an 8-week safety follow-up.Fasting LDL-C (OSR6183, Beckman Coulter), HDL cholesterol (HDL-C, OSR6187, Beckman Coulter), total cholesterol (OSR6116, Beckman Coulter) and triglycerides (OSR61118, Beckman Coulter) concentrations were measured by commercial kits on a Beckman Coulter AU600 Chemistry Analyzer. Non-HDL cholesterol (non-HDL-C) concentration was calculated by subtracting HDL-C concentration from total cholesterol concentration. Very low density lipoprotein cholesterol (vLDL-C) concentration was calculated by dividing the triglyceride concentration by 5 (when triglyceride < 4.52 mmol/L) or by subtracting HDL-C and LDL-C concentration from total cholesterol concentration (when triglyceride ≥4.52 mmol/L). Apolipoprotein A1, apolipoprotein B and lipoprotein(a) concentrations were determined using a nephelometric method (OUED, OSAN and OQHL, respectively, Siemens BN ProSpec System). We measured unbound PCSK9 concentrations using an in-house developed enzyme-linked immunosorbent assay. All lipids and PCSK9 were tested in a central laboratory (WuXi AppTec, DNA extracted from blood samples of all enrolled participants were sequenced by Novogene (