TY - JOUR
T1 - Cognitive function in a randomized trial of evolocumab
AU - EBBINGHAUS Investigators
AU - Giugliano, Robert P.
AU - Mach, François
AU - Zavitz, Kenton
AU - Kurtz, Christopher
AU - Im, Kyungah
AU - Kanevsky, Estella
AU - Schneider, Jingjing
AU - Wang, Huei
AU - Keech, Anthony
AU - Pedersen, Terje R.
AU - Sabatine, Marc S.
AU - Sever, Peter S.
AU - Robinson, Jennifer G.
AU - Honarpour, Narimon
AU - Wasserman, Scott M.
AU - Ott, Brian R.
A2 - Stuķēna, Inga
N1 - Inga Stuķēna as well as a complete list of investigators is provided in the Supplementary Appendix, available at NEJM.org.
https://www.nejm.org/doi/suppl/10.1056/NEJMoa1701131/suppl_file/nejmoa1701131_appendix.pdf
Funding Information:
(Funded by Amgen; EBBINGHAUS ClinicalTrials.gov number, NCT02207634.) Supported by Amgen. We thank Sarah T. Farias, Ph.D., at UC Davis Health for providing the English-language and translated versions of the Everyday Cognition (ECog) tool.
Publisher Copyright:
Copyright © 2017 Massachusetts Medical Society.
PY - 2017/8/17
Y1 - 2017/8/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85027494280&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/28813214/
U2 - 10.1056/NEJMoa1701131
DO - 10.1056/NEJMoa1701131
M3 - Article
C2 - 28813214
AN - SCOPUS:85027494280
SN - 0028-4793
VL - 377
SP - 633
EP - 643
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 7
ER -