PCSK9i does not negatively influence cognitive functioning in children with HeFH

RCTs among adults with HeFH show that treatment with evolocumab does not lead to cognitive dysfunction. But does the same hold true for pediatric patients with HeFH? This post-hoc analysis of data from the HAUSER-RCT study offers more insight.

Cognitive function with evolocumab in pediatric heterozygous familial hypercholesterolemia
Literature - Gaudet D, Ruzza A, Bridges I, et al. - J Clin Lipidol. 2022 Jul 21:S1933-2874(22)00210-0. doi: 10.1016/j.jacl.2022.07.005.

Introduction and methods

Background

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 [1]. 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.

Methods

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).

Outcomes

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.

Main results

• 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.

Conclusion

References

Find this article online at J Clin Lipidol.