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Alirocumab treatment and neurocognitive function according to the CANTAB scale in patients at increased
Matthew J Janik1, Dorothea V Urbach2, Elane van Nieuwenhuizen3
1Department of Cardiology, Wilmington Health, Wilmington, NC, USA.
Insights
Alirocumab, a PCSK9 inhibitor, effectively lowers LDL-C and cardiovascular risk without impacting neurocognitive function in high-risk patients. This study confirms its safety and efficacy in managing hypercholesterolemia.
Area of Science:
- Cardiology
- Neuroscience
- Pharmacology
Background:
- Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors like alirocumab significantly reduce LDL-C and cardiovascular events.
- The effect of sustained low LDL-C on neurocognitive function remains unclear, with some lipid-lowering therapies linked to cognitive issues.
Purpose of the Study:
- To evaluate the impact of alirocumab on neurocognitive function in patients with hypercholesterolemia.
- To confirm the cardiovascular benefits and safety profile of alirocumab in high-risk populations.
Main Methods:
- A double-blind, placebo-controlled trial involving 2176 patients with heterozygous familial hypercholesterolemia or non-FH at high cardiovascular risk.
- Patients received subcutaneous alirocumab (75/150 mg) or placebo every two weeks for 96 weeks.
- Neurocognitive function was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB), with Spatial Working Memory Strategy (SWMS) as the primary outcome.
Main Results:
- Alirocumab demonstrated noninferiority to placebo in SWMS z-score change over 96 weeks, indicating no adverse effect on working memory.
- Exploratory neurocognitive assessments also showed no significant differences between treatment groups.
- Alirocumab achieved significant reductions in LDL-C and other lipid parameters and was well-tolerated.
Conclusions:
- Alirocumab treatment for 96 weeks did not negatively impact neurocognitive function in high-risk patients.
- The study confirms alirocumab's efficacy in lowering LDL-C and its favorable safety profile, consistent with prior PCSK9 inhibitor data.
Background And Aims:
Trials of the fully human monoclonal antibody proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9) alirocumab in hypercholesterolemia demonstrated substantial low-density lipoprotein cholesterol (LDL-C) lowering, reduction in cardiovascular (CV) events and outcomes, and a generally acceptable safety and tolerability profile. The impact of maintaining low LDL-C levels on higher order brain function is unclear, with reports of neurocognitive disorders with other lipid-lowering therapies.
Methods:
Patients (n = 2176) with heterozygous familial hypercholesterolemia (HeFH) or non-FH, at high or very-high CV risk despite maximally tolerated statin therapy, randomly received subcutaneous alirocumab 75/150 mg or placebo every 2 weeks in this double-blind, placebo-controlled trial. The primary outcome was prospectively evaluated every 24 weeks over 96 weeks by Cambridge Neuropsychological Test Automated Battery (CANTAB).
Results:
Among 2086 patients with CANTAB cognitive domain Spatial Working Memory Strategy (SWMS) assessments, change from baseline to Week 96 in SWMS z-score (primary outcome) achieved noninferiority between alirocumab and placebo (least squares [LS] mean change at Week 96, -0.180 vs -0.200; LS mean difference vs placebo [95% confidence interval]: -0.020 [-0.094 to 0.055], p = 0.6055). Exploratory outcome measures, which further assessed neurocognitive function in the CANTAB domains, did not differ significantly over 96 weeks and achieved nominal noninferiority between treatment groups. Alirocumab resulted in nominally significant reductions in LDL-C and other lipid parameters, and was generally well tolerated.
Conclusions:
Confirming previous PCSK9 inhibitor data, alirocumab showed no effect on neurocognitive function over 96 weeks' treatment, substantially reduced LDL-C and was generally well tolerated in patients with HeFH or non-FH at high or very-high CV risk.
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