Does Lowering LDL with Evolocumab Impact Cognitive Function?

The primary endpoint was change from baseline score of spatial working memory strategy index of executive function
The primary endpoint was change from baseline score of spatial working memory strategy index of executive function

WASHINGTON, DC—Researchers presented results from a trial evaluating the impact of evolocumab on cognitive function in patients enrolled in the FOURIER study at the ACC.17 Scientific Session.

Evolocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, is approved as adjunct to diet and maximally tolerated statin therapy for treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD), who require additional lowering of low-density lipoprotein cholesterol (LDL-C); and as adjunct to other LDL-lowering therapies (eg, statins, ezetimibe, LDL apheresis) in patients with homozygous familial hypercholesterolemia (HoFH) who require additional lowering of LDL-C.

The EBBINGHAUS study, a double-blind, placebo-controlled randomized non-inferiority trial, included a cohort of 1,204 patients. The primary endpoint was the change from baseline score of spatial working memory strategy index of executive function in evolocumab and placebo groups.

Results showed a similar change in baseline raw score of spatial working memory strategy index of executive function in the evolocumab and placebo groups (mean change from baseline –0.2 vs. –0.3, respectively), assessed by the Cambridge Neuropsychological Test Automated Battery (CANTAB) Spatial Working Memory strategy index of executive function.

There were three secondary endpoints; changes in working memory, memory function and psychomotor speed. Results for each of these showed a similar change from baseline for evolocumab and placebo. Specifically, the spatial working memory between-errors score: evolocumab –0.5 vs. placebo –0.9 (baseline 21.0); paired associates learning total errors adjusted: evolocumab –1.5 vs. placebo –1.5 (baseline 25.8); RTI median five-choice reaction time: 5.2 milliseconds with evolocumab vs. 0.9 milliseconds with placebo (baseline 355.9).  

Neurocognitive adverse events, in the full cohort, were reported for 19 (1.9%) in the evolocumab group, compared to 16 (1.6%) in the placebo group. 

"There has long been a debate that low LDL cholesterol levels could lead to negative effects on memory or other cognitive functions," saidRobert P. Giugliano, M.D., S.M., Brigham and Women's Hospital, Boston and lead study investigator. "We did not find evidence for a decline in neurocognitive function after nearly two years of treatment with evolocumab using a dedicated series of neuropsychologic tests. We also asked patients and their physicians to provide their assessments and found no differences between evolocumab and placebo. These findings provide strong support for the safety of reducing LDL with evolocumab to levels well below current treatment targets."