Cognitive Function in a Randomized Trial of Evolocumab

R. P. Giugliano, F. Mach, K. Zavitz, C. Kurtz, K. Im, E. Kanevsky, J. Schneider, H. Wang, A. Keech, T. R. Pedersen, M. S. Sabatine, P. S. Sever, J. G. Robinson, N. Honarpour, S. M. Wasserman, B. R. Ott, EBBINGHAUS Investigators

Research output: Contribution to journalArticlepeer-review

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
Original languageEnglish
Pages (from-to)633-643
Number of pages11
JournalNew England Journal of Medicine
Volume377
Issue number7
DOIs
Publication statusPublished - Aug 17 2017
Externally publishedYes

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal/adverse effects/therapeutic use
  • Anticholesteremic Agents/adverse effects/therapeutic use
  • Atherosclerosis/drug therapy/psychology
  • Cholesterol, LDL/blood
  • Cognition/drug effects
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
  • Male
  • Memory/drug effects
  • Middle Aged
  • Proprotein Convertase 9/antagonists & inhibitors
  • Prospective Studies
  • Psychological Tests
  • Self-Assessment

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