Cognition After Lowering LDL-Cholesterol With Evolocumab.


Journal

Journal of the American College of Cardiology
ISSN: 1558-3597
Titre abrégé: J Am Coll Cardiol
Pays: United States
ID NLM: 8301365

Informations de publication

Date de publication:
12 05 2020
Historique:
received: 02 12 2019
revised: 25 02 2020
accepted: 10 03 2020
entrez: 9 5 2020
pubmed: 10 5 2020
medline: 31 12 2020
Statut: ppublish

Résumé

The EBBINGHAUS (Evaluating PCSK9 Binding Antibody Influence on Cognitive Health in High Cardiovascular Risk Subjects) trial demonstrated that evolocumab added to a background statin did not affect cognitive performance in a subset of 1,204 patients enrolled in FOURIER (Further Cardiovascular Outcomes Research With PCSK9 inhibitors in Subjects With Elevated Risk). The authors describe patient-reported cognition in the entire FOURIER trial using a self-survey. FOURIER was a randomized, double-blind, placebo-controlled trial involving patients with atherosclerotic cardiovascular disease and low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dl or non-high-density cholesterol ≥100 mg/dl despite statin therapy. At the final visit, patients completed a 23-item survey on memory and executive domains from the Everyday Cognition (ECog) scale. Patients compared their levels of everyday function at the end of the trial with their levels at the beginning and scored as 1 (no change or improvement), 2 (occasionally worse), 3 (consistently little worse), or 4 (consistently much worse). ECog scores were compared by the 2 randomized treatment arms and by achieved LDL-C at 4 weeks. A total of 22,655 patients completed ECog after a median duration of 2.2 years. The proportions of patients reporting cognitive decline (ECog score ≥2) at the end of the study were similar for placebo versus evolocumab, both for total score 3.6% versus 3.7% (p = 0.62) and for subdomains (memory, 5.8% vs. 6.0%; total executive, 3.6% vs. 3.7%). The proportion of patients reporting a decline in total cognitive score was similar among the 2,338 patients who achieved very low LDL-C levels (<20 mg/dl) compared to the 3,613 patients with LDL-C ≥100 mg/dl (3.8% vs. 4.5%, p = 0.57). The addition of evolocumab to maximally tolerated statin therapy had no impact on patient-reported cognition after an average of 2.2 years of treatment, even among patients who achieved LDL-C <20 mg/dl.

Sections du résumé

BACKGROUND
The EBBINGHAUS (Evaluating PCSK9 Binding Antibody Influence on Cognitive Health in High Cardiovascular Risk Subjects) trial demonstrated that evolocumab added to a background statin did not affect cognitive performance in a subset of 1,204 patients enrolled in FOURIER (Further Cardiovascular Outcomes Research With PCSK9 inhibitors in Subjects With Elevated Risk).
OBJECTIVES
The authors describe patient-reported cognition in the entire FOURIER trial using a self-survey.
METHODS
FOURIER was a randomized, double-blind, placebo-controlled trial involving patients with atherosclerotic cardiovascular disease and low-density lipoprotein cholesterol (LDL-C) levels ≥70 mg/dl or non-high-density cholesterol ≥100 mg/dl despite statin therapy. At the final visit, patients completed a 23-item survey on memory and executive domains from the Everyday Cognition (ECog) scale. Patients compared their levels of everyday function at the end of the trial with their levels at the beginning and scored as 1 (no change or improvement), 2 (occasionally worse), 3 (consistently little worse), or 4 (consistently much worse). ECog scores were compared by the 2 randomized treatment arms and by achieved LDL-C at 4 weeks.
RESULTS
A total of 22,655 patients completed ECog after a median duration of 2.2 years. The proportions of patients reporting cognitive decline (ECog score ≥2) at the end of the study were similar for placebo versus evolocumab, both for total score 3.6% versus 3.7% (p = 0.62) and for subdomains (memory, 5.8% vs. 6.0%; total executive, 3.6% vs. 3.7%). The proportion of patients reporting a decline in total cognitive score was similar among the 2,338 patients who achieved very low LDL-C levels (<20 mg/dl) compared to the 3,613 patients with LDL-C ≥100 mg/dl (3.8% vs. 4.5%, p = 0.57).
CONCLUSIONS
The addition of evolocumab to maximally tolerated statin therapy had no impact on patient-reported cognition after an average of 2.2 years of treatment, even among patients who achieved LDL-C <20 mg/dl.

Identifiants

pubmed: 32381158
pii: S0735-1097(20)34654-4
doi: 10.1016/j.jacc.2020.03.039
pii:
doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0
Anticholesteremic Agents 0
Cholesterol, LDL 0
Hydroxymethylglutaryl-CoA Reductase Inhibitors 0
evolocumab LKC0U3A8NJ

Types de publication

Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2283-2293

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Auteurs

Baris Gencer (B)

TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

François Mach (F)

Cardiology Division, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland.

Jianping Guo (J)

TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

KyungAh Im (K)

TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Andrea Ruzza (A)

AMGEN, Thousand Oaks, California.

Huei Wang (H)

AMGEN, Thousand Oaks, California.

Christopher E Kurtz (CE)

AMGEN, Thousand Oaks, California.

Terje Rolf Pedersen (TR)

Department of Preventive Cardiology, Oslo University Hospital, Aker and Medical Faculty, University of Oslo, Oslo, Norway.

Anthony C Keech (AC)

Sydney Medical School, NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia.

Brian R Ott (BR)

Rhode Island Hospital, Brown University, Providence, Rhode Island.

Marc S Sabatine (MS)

TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Robert P Giugliano (RP)

TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: rgiugliano@bwh.harvard.edu.

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Classifications MeSH