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Cognition After Lowering LDL Cholesterol With Evolocumab
Quick Takes
- Neither evolocumab nor LDL cholesterol level was associated with impaired patient-reported cognition.
- Since patient-reported adverse effects from statin medications occur at a higher frequency than adverse effects seen in clinical trials, the patient-reported findings in this study could improve acceptance of PCSK9 inhibitors.
- This study reflects only a single cognitive assessment, so more data are needed to fully characterize the long-term cognitive effects of PCSK9 inhibitors, such as evolocumab.
Study Questions:
What are the effects of evolocumab and low low-density lipoprotein (LDL) cholesterol on patient-reported cognition?
Methods:
This work was done as part of the FOURIER trial, which compared evolocumab to placebo in patients with atherosclerotic cardiovascular disease. The authors measured patient-reported cognition at the final research visit using an abbreviated Everyday Cognition (ECog) scale, focused on memory and executive function. Patients compared their current cognitive performance to their cognitive function at the beginning of the study on a 4-point scale for each item. The authors analyzed ECog responses based on treatment group (evolocumab vs. placebo) and LDL cholesterol value at 4 weeks, regardless of treatment assignment.
Results:
There were 22,655 patients included in these analyses, representing 82% of the FOURIER trial participants. The median follow-up time was 2.2 years. A decline in memory was reported in about 6% of subjects and a decline in executive function was reported in about 3% of subjects. There were no differences in reported cognition between the evolocumab and placebo groups. When subjects were stratified by LDL cholesterol level, 4 weeks into the study, there was no difference between the various quintiles in memory or executive function.
Conclusions:
Neither very low LDL cholesterol level nor evolocumab was associated with a decline in patient-reported memory or executive function.
Perspective:
Cerebrovascular disease is a large contributor to not only dementia, but also impaired cognition. Lower LDL cholesterol values are associated with a decreased risk of stroke. Despite a lack of clear data, there is some concern that statins impair cognition. It is unclear if this possible effect is due to the LDL cholesterol-lowering effects of statin therapy or other non–cholesterol-lowering effects. With the approval of proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors, and the potential for markedly lower LDL cholesterol levels, there are questions if these drugs, and very low LDL cholesterol levels, are associated with impaired cognition. A prior study showed no association between cognitive function and evolocumab on objective, computer-based cognitive testing; however, this is the first study to look at patient-reported cognition and PCSK9 inhibitors. Given patients’ concerns about adverse effects from statins, this patient-centered approach, showing no association between evolocumab and impaired cognition, is important. This study also demonstrated that LDL cholesterol levels, irrespective of treatment assignment, were not associated with worsening cognition. Since cognition was only evaluated at a single point in time and only reflects an approximately 2-year exposure to evolocumab, longer-term data would be helpful to confirm these findings.
Clinical Topics: Cardiovascular Care Team, Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Vascular Medicine, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Sleep Apnea
Keywords: Antibodies, Monoclonal, Atherosclerosis, Cerebrovascular Disorders, Cholesterol, LDL, Cognition, Dementia, Dyslipidemias, Executive Function, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Memory, PCSK9 protein, human, Primary Prevention, Proprotein Convertase 9, Stroke, Vascular Diseases
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