Cognitive Function in a Randomized Trial of Evolocumab
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
BACKGROUND
Findings from clinical trials of proprotein convertase subtilisin–kexin type 9 (PCSK9)
inhibitors have led to concern that these drugs or the low levels of low-density lipoprotein
(LDL) cholesterol that result from their use are associated with cognitive deficits.
METHODS
In a subgroup of patients from a randomized, placebo-controlled trial of evolocumab
added to statin therapy, we prospectively assessed cognitive function using the Cambridge
Neuropsychological Test Automated Battery. The primary end point was the score on the
spatial working memory strategy index of executive function (scores range from 4 to 28,
with lower scores indicating a more efficient use of strategy and planning). Secondary end
points were the scores for working memory (scores range from 0 to 279, with lower scores
indicating fewer errors), episodic memory (scores range from 0 to 70, with lower scores
indicating fewer errors), and psychomotor speed (scores range from 100 to 5100 msec,
with faster times representing better performance). Assessments of cognitive function
were performed at baseline, week 24, yearly, and at the end of the trial. The primary
analysis was a noninferiority comparison of the mean change from baseline in the score
on the spatial working memory strategy index of executive function between the patients
who received evolocumab and those who received placebo; the noninferiority margin was
set at 20% of the standard deviation of the score in the placebo group.
RESULTS
A total of 1204 patients were followed for a median of 19 months; the mean (±SD) change
from baseline over time in the raw score for the spatial working memory strategy index
of executive function (primary end point) was −0.21±2.62 in the evolocumab group and
−0.29±2.81 in the placebo group (P<0.001 for noninferiority; P=0.85 for superiority).
There were no significant between-group differences in the secondary end points of
scores for working memory (change in raw score, −0.52 in the evolocumab group and
−0.93 in the placebo group), episodic memory (change in raw score, −1.53 and −1.53,
respectively), or psychomotor speed (change in raw score, 5.2 msec and 0.9 msec, respectively).
In an exploratory analysis, there were no associations between LDL cholesterol
levels and cognitive changes.
CONCLUSIONS
In a randomized trial involving patients who received either evolocumab or placebo in
addition to statin therapy, no significant between-group difference in cognitive function
was observed over a median of 19 months.
Findings from clinical trials of proprotein convertase subtilisin–kexin type 9 (PCSK9)
inhibitors have led to concern that these drugs or the low levels of low-density lipoprotein
(LDL) cholesterol that result from their use are associated with cognitive deficits.
METHODS
In a subgroup of patients from a randomized, placebo-controlled trial of evolocumab
added to statin therapy, we prospectively assessed cognitive function using the Cambridge
Neuropsychological Test Automated Battery. The primary end point was the score on the
spatial working memory strategy index of executive function (scores range from 4 to 28,
with lower scores indicating a more efficient use of strategy and planning). Secondary end
points were the scores for working memory (scores range from 0 to 279, with lower scores
indicating fewer errors), episodic memory (scores range from 0 to 70, with lower scores
indicating fewer errors), and psychomotor speed (scores range from 100 to 5100 msec,
with faster times representing better performance). Assessments of cognitive function
were performed at baseline, week 24, yearly, and at the end of the trial. The primary
analysis was a noninferiority comparison of the mean change from baseline in the score
on the spatial working memory strategy index of executive function between the patients
who received evolocumab and those who received placebo; the noninferiority margin was
set at 20% of the standard deviation of the score in the placebo group.
RESULTS
A total of 1204 patients were followed for a median of 19 months; the mean (±SD) change
from baseline over time in the raw score for the spatial working memory strategy index
of executive function (primary end point) was −0.21±2.62 in the evolocumab group and
−0.29±2.81 in the placebo group (P<0.001 for noninferiority; P=0.85 for superiority).
There were no significant between-group differences in the secondary end points of
scores for working memory (change in raw score, −0.52 in the evolocumab group and
−0.93 in the placebo group), episodic memory (change in raw score, −1.53 and −1.53,
respectively), or psychomotor speed (change in raw score, 5.2 msec and 0.9 msec, respectively).
In an exploratory analysis, there were no associations between LDL cholesterol
levels and cognitive changes.
CONCLUSIONS
In a randomized trial involving patients who received either evolocumab or placebo in
addition to statin therapy, no significant between-group difference in cognitive function
was observed over a median of 19 months.
Date Issued
2017-08-17
Date Acceptance
2017-08-01
Citation
NEW ENGLAND JOURNAL OF MEDICINE, 2017, 377 (7), pp.633-643
ISSN
0028-4793
Publisher
Massachusetts Medical Society
Start Page
633
End Page
643
Journal / Book Title
NEW ENGLAND JOURNAL OF MEDICINE
Volume
377
Issue
7
Copyright Statement
© 2017 Massachusetts Medical Society.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000407691400006&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
General & Internal Medicine
SPATIAL WORKING-MEMORY
CARDIOVASCULAR EVENTS
REDUCING LIPIDS
SAFETY
DISEASE
RATIONALE
EFFICACY
DESIGN
RISK
METAANALYSIS
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal
Anticholesteremic Agents
Atherosclerosis
Cholesterol, LDL
Cognition
Double-Blind Method
Drug Therapy, Combination
Female
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Male
Memory
Middle Aged
Proprotein Convertase 9
Prospective Studies
Psychological Tests
Self-Assessment
EBBINGHAUS Investigators
11 Medical And Health Sciences
Publication Status
Published