ESPEYB15 12 Type 2 Diabetes, Metabolic Syndrome and Lipid Metabolism Important for clinical practice (1) (1 abstracts)
12.14 Cognitive Function in a Randomized Trial of Evolocumab
Giugliano RP , Mach F , Zavitz K , Kurtz C , Im K , Kanevsky E , Schneider J , Wang H , Keech A , Pedersen TR , Sabatine MS , Sever PS , Robinson JG , Honarpour N , Wasserman SM , Ott BR & EBBINGHAUS Investigators
Thrombolysis in Myocardial Infarction Study Group, Brigham and Women’s Hospital, Boston MA, USA
To read the full abstract: N Engl J Med 2017;377:633-643
Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates levels of plasma LDL-C by interacting with the LDL receptor. After binding and internalization, PCSK9 directs the LDL receptor to lysosomal degradation and inhibits its recycling to the cell surface, and thus accelerates the degradation of hepatic LDL receptors. This reduces the capacity of the liver to remove LDL-C from the circulation. Evolocumab, a monoclonal antibody against PCSK9, substantially reduces LDL-C levels. However, given the importance of cholesterol in synapse formation and function, the potential adverse cognitive effects of cholesterol-reducing drugs are a reasonable concern, particularly in the case of lipophilic statins that are able to cross the blood–brain barrier.14 Data from several sources have suggested that low levels of either LDL-C or the monoclonal antibodies may be associated with impaired cognitive function.
Here, Giugliano et al. prospectively evaluated cognition in patients with clinically evident atherosclerosis. The mean age of the patients was 63 years, 72% were men. At the time of randomization, median LDL-C was 92 mg/dl (2.40 mmol/l). Evolocumab, as compared with placebo, neither improved nor worsened executive function, working memory, episodic memory or psychomotor speed. Similar findings were also demonstrated in 661 patients in the evolocumab group who had an LDL-C <25 mg/dl. Of note, the follow up period was short. Thus, we will have to wait for the ongoing 5-year extension of the trial in approximately 500 patients. The findings of the long term study are particularly important as a dedicated study, HAUSER-RCT, is being conducted to examine the efficacy and safety of evolocumab in pediatric patients with heterozygous familial hypercholesterolemia.15
14. P. GR, Francois M, Kenton Z, Christopher K, Jingjing S, Huei W et al. Design and rationale of the EBBINGHAUS trial: A phase 3, double-blind, placebo-controlled, multicenter study to assess the effect of evolocumab on cognitive function in patients with clinically evident cardiovascular disease and receiving statin background lipid-lowering therapy—A cognitive study of patients enrolled in the FOURIER trial. Clinical Cardiology 2017; 40(2): 59-65.
15. Gaudet D, Langslet G, Gidding SS, Luirink IK, Ruzza A, Kurtz C et al. Efficacy, safety, and tolerability of evolocumab in pediatric patients with heterozygous familial hypercholesterolemia: Rationale and design of the HAUSER-RCT study. Journal of Clinical Lipidology 2018.
Volume 15
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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