Author + information
- Received December 2, 2019
- Revision received February 25, 2020
- Accepted March 10, 2020
- Published online May 4, 2020.
- Baris Gencer, MDa,
- François Mach, MDb,
- Jianping Guo, MSa,
- KyungAh Im, PhDa,
- Andrea Ruzza, MD, PhDc,
- Huei Wang, PhDc,
- Christopher E. Kurtz, MDc,
- Terje Rolf Pedersen, MD, PhDd,
- Anthony C. Keech, MDe,
- Brian R. Ott, MDf,
- Marc S. Sabatine, MD, MPHa,
- Robert P. Giugliano, MD, SMa,∗ (, )@BrighamWomens@TIMIStudyGroup@rgiugliano,
- on behalf of the FOURIER Investigators
- aTIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
- bCardiology Division, Department of Medicine, Geneva University Hospitals, Geneva, Switzerland
- cAMGEN, Thousand Oaks, California
- dDepartment of Preventive Cardiology, Oslo University Hospital, Aker and Medical Faculty, University of Oslo, Oslo, Norway
- eSydney Medical School, NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia
- fRhode Island Hospital, Brown University, Providence, Rhode Island
- ↵∗Address for correspondence:
Dr. Robert P. Giugliano, TIMI Study Group, Brigham and Women’s Hospital, Hale BTM, Suite 7022, 60 Fenwood Road, Boston, Massachusetts 02115.
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.
The FOURIER trial was supported by a research grant from Amgen. The FOURIER trial was designed, conducted, and managed in a collaborative effort between the FOURIER executive and steering committees, the FOURIER investigators, and the sponsor, Amgen. The sponsor also collected the data. However, Amgen played no role in the analysis and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr. Gencer’s activities in the TIMI Group, Harvard Medical School, are supported by grants from the Geneva University Hospitals, Eugenio Litta and Arthemis Foundations. Dr. Mach has received grants to the institution from Amgen, AstraZeneca, Eli Lilly, Merck Sharp & Dohme, Novartis, Sanofi, and Pfizer. Mr. Guo and Dr. Im are members of the TIMI Study Group, which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Amgen, Aralez, AstraZeneca, Bayer HealthCare Pharmaceuticals, Brahms, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Intarcia, Janssen, MedImmune, Merck, Novartis, Pfizer, Poxel, Quark Pharmaceuticals, Roche, Takeda, The Medicines Company, and Zora Biosciences. Drs. Ruzza, Wang, and Kurtz are employed by and own stock in Amgen. Dr. Keech has received honoraria from Abbott and Amgen; has received consulting and Advisory Board fees from Abbott and Amgen; has received lecture fees from AstraZeneca and Pfizer; and has received support for an educational activity from Mylan. Dr. Pederson has received Speakers Bureau fees from Amgen, Boehringer Ingelheim, and Sanofi; and has received consulting and Advisory Board fees from Amgen, Merck, and Sanofi. Dr. Ott has received consulting fees from Amgen. Dr. Sabatine has received research grant support through Brigham and Women’s Hospital from Abbott Laboratories, Amgen, AstraZeneca, Critical Diagnostics, Daiichi-Sankyo, Eisai, Genzyme, Gilead, GlaxoSmithKline, Intarcia, Janssen Research and Development, The Medicines Company, MedImmune, Merck, Novartis, Poxel, Pfizer, Roche Diagnostics, and Takeda; and has received personal fees from Alnylam, Bristol-Myers Squibb, CVS Caremark, Dynamix, Esperion, Ionis, and MyoKardia. Dr. Giugliano has received grants from Amgen; has received honoraria from Amgen, Daiichi-Sankyo, and Merck; and has received consulting fees from Amgen, Akcea, Amarin, Boehringer Ingelheim, Bristol-Myers Squibb, CVS Caremark, Daiichi-Sankyo, Esperion, GlaxoSmithKline, Lexicon, Merck, Portola, Pfizer, and Servier.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC author instructions page.
- Received December 2, 2019.
- Revision received February 25, 2020.
- Accepted March 10, 2020.
- 2020 American College of Cardiology Foundation
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