Statistical analysis
EVENTS, EVENT, SECONDARY, ADVERSE EVENT
Assuming a common standard deviation of 40% and a dropout rate of 10%, the sample size of 148 participants was sufficient to generate 99% power to detect ≥40% LDL-C reductions [Efficacy endpoints were analyzed in the efficacy analysis population, defined as participants who received at least one dose of tafolecimab or placebo and had at least one post-baseline assessment. Two estimands, the on-treatment estimand and the treatment policy estimand, were used to assess treatment efficacy from different perspectives and accounted for intercurrent events differently [The on-treatment estimand assesses treatment efficacy prior to the intercurrent events like study drug discontinuation or background statin therapy adjustment. For continuous endpoints, mixed model for repeated measures method was used, with baseline value, baseline-by-visit interaction, visit, treatment, visit-by-treatment interaction and randomization stratification factors as fixed effects and unstructured covariance. For categorical endpoints, Clopper-Pearson method [The treatment policy estimand assesses treatment efficacy regardless of any intercurrent event. For continuous endpoints, pattern-mixture model method was used for missing data imputation and analysis of covariance (ANCOVA) was used for analysis of imputed data. For categorical endpoints, statistical testing methods were the same as those of the on-treatment estimand except that participants without any available assessment at week 12 were treated as non-responders.The primary endpoint (the percent change from baseline to week 12 in LDL-C levels) and key secondary endpoints (proportion of participants achieving ≥50% LDL-C reductions and proportion of participants with LDL-C level <1.8 mmol/L at week 12) were assessed by both on-treatment and treatment policy estimands, and controlled for type I error. The percent change from baseline to week 12 in non-HDL-C, apolipoprotein B and lipoprotein (a) levels were assessed by on-treatment estimand. Other efficacy endpoints were reported descriptively.Safety analyses were done on the safety analysis population, defined as all participants who received at least one dose of tafolecimab or placebo. Adverse events were descriptively summarized.Exploratory analyses were done to evaluate the effects of All statistical analyses were performed with SAS version 9.4.