PCSK9i does not negatively influence cognitive functioning in children with HeFH
Cognitive function with evolocumab in pediatric heterozygous familial hypercholesterolemia
Introduction and methods
The HAUSER-RCT study showed that in pediatric patients with heterozygous familial hypercholesterolemia (HeFH), treatment with the PCSK9 inhibitor evolocumab for 24 weeks is safe and lowers LDL-c and other lipid parameter levels, compared with placebo . In addition, randomized trials among adults with HeFH demonstrated that treatment with evolocumab does not lead to cognitive dysfunction [2,3]. However, it is unknown whether the latter is also true in pediatric patients with HeFH.
Aim of the study
The aim of this post-hoc analysis of data from the HAUSER-RCT study was to investigate whether treatment with evolocumab for 24 weeks influences cognitive functioning in pediatric patients with HeFH.
The researchers conducted a post-hoc analysis of data from the HAUSER-RCT study. In this multicenter, double-blind, placebo-controlled phase 3 study, 157 pediatric patients aged 10-17 years with HeFH were randomized (2:1 ratio) to monthly, subcutaneous treatment with evolocumab 420 mg or placebo for 24 weeks. Inclusion criteria were LDL-c levels ≥3.4 mmol/L, triglyceride levels ≤4.5 mmol/L and stable lipid-lowering therapy for at least 4 weeks before screening. At baseline and after 24 weeks, 4 domains of cognitive functioning were examined using Cogstate tests, namely: psychomotor function (Detection test), attention (Identification test), visual learning (One-Card Learning Test) and executive functions (Groton Maze Learning Test).
The researchers were interested in between-group differences in age-standardized mean cognitive test score changes from baseline to week 24. After 24 weeks, data were missing for 9/104 (9%) patients in the evolocumab group and for 8/53 (15%) patients in the placebo group; missing data were not interpolated.
- After 24 weeks, baseline-adjusted, age-standardized differences between the treatment groups,expressed as least squares mean (LSM), for psychomotor function (Detection test), attention (Identification test), visual learning (One-Card Learning Test) and executive function (Groton Maze Learning Test) were 0.3 (95%CI: -0.1 to 0.8), 0.3 (95%CI: 0.0 to 0.7), -0.1 (95%CI: -0.5 to0.4) and 0.1 (95%CI: -0.2 to 0.4), respectively. Where a positive change in LSM indicated a more beneficial result in the evolocumab group compared with the placebo group.
- Effect sizes expressing the magnitude of the between-group differences in baseline-adjusted, age-standardized mean test score changes at week 24 suggest a small positive effect of evolocumab on attention (Cohen's d=0.5) and psychomotor function (Cohen's d=0.3), and a trivial effect of evolocumab on executive function (Cohen's d=0.1) and visual learning (Cohen's d=-0.1).
- For all cognitive tests, abnormal cognitive decline (reliable change index [RCI] ≤-1.65) occurred less often in the evolocumab group than in the placebo group.
- Clinically important cognitive decline (RCI ≤-1.65 on at least two cognitive tests ) at an individual level occurred in 1% of the of patients in the evolocumab group and in 11% of patients in the placebo group.
This post-hoc analysis of data from the HAUSER-RCT study shows that treatment with evolocumab for 24 weeks does not negatively influence cognitive functioning in pediatric patients with HeFH.