Long-Term Cognitive Safety of Achieving Very Low LDL Cholesterol with Evolocumab
Zimerman A, O'Donoghue ML, Ran X, Im K, Ott BR, Mach F, Zavitz K, Kurtz CE, Monsalvo ML, Wang B, Atar D, Keech A, Sabatine MS, Giugliano RP
NEJM evidence · 16 citas
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Cómo se estudió
- Diseño
- Ensayo controlado aleatorizado (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiación no declarada
Publicación
- Publicado
- 2024-12-24 · NEJM Evid · vol. 4 · número 1 · pág. EVIDoa2400112
- Citado
- 23 citas · más que el 99% de estudios similares · 8.9× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 27 trabajos
- Acceso
- De pago
- Áreas de investigación
- Lipoproteins and Cardiovascular Health · Cholesterol and Lipid Metabolism · Dementia and Cognitive Impairment Research
- Palabras clave
- evolocumab, PCSK9 inhibition, very low LDL cholesterol, cognitive safety, executive function, spatial working memory, atherosclerotic cardiovascular disease, statin therapy, open-label extension, long-term cognitive outcomes, dementia risk
- MeSH
- humans, antibodies, monoclonal, anticholesteremic agents, prospective studies, cognition, aged, middle aged, female, male, cholesterol, ldl, antibodies, monoclonal, humanized
14 autores
- André Zimerman🇺🇸🇧🇷Brigham and Women's Hospital; Harvard University; Hospital Moinhos de Vento; Thrombolysis in Myocardial Infarction Study Group
- Michelle L. O’Donoghue🇺🇸Brigham and Women's Hospital; Harvard University; Thrombolysis in Myocardial Infarction Study Group
- Xinhui Ran🇺🇸Brigham and Women's Hospital; Harvard University; Thrombolysis in Myocardial Infarction Study Group
- KyungAh Im🇺🇸Brigham and Women's Hospital; Harvard University; Thrombolysis in Myocardial Infarction Study Group
- Brian R. Ott🇺🇸Brown University
- François Mach🇨🇭University Hospital of Geneva
- Kenton H. Zavitz🇬🇧Cambridge Cognition (United Kingdom)
- Christopher E. Kurtz
- Maria Laura Monsalvo🇺🇸Amgen (United States)
- Bei Wang🇺🇸Amgen (United States)
- Dan Atar🇳🇴Oslo University Hospital; University of Oslo
- ANTHONY C. KEECH🇦🇺The University of Sydney; National Health and Medical Research Council
- Marc Steven Sabatine🇺🇸Brigham and Women's Hospital; Harvard University; Thrombolysis in Myocardial Infarction Study Group
- Robert Patrick Giugliano🇺🇸Brigham and Women's Hospital; Harvard University; Thrombolysis in Myocardial Infarction Study Group
Resumen
El texto original del estudio, en el idioma en que se publicó.
Background
Concerns persist regarding the cognitive safety of achieving very low levels of low-density lipoprotein (LDL) cholesterol. Although short-term studies are reassuring, the long-term cognitive effects of sustained exposure to very low LDL cholesterol levels through combined proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibition and statin therapy remain unknown.
Methods
This prospective study enrolled a subset of adults with atherosclerotic cardiovascular disease who had completed a neurocognitive substudy (EBBINGHAUS) of a placebo-controlled randomized trial of evolocumab (FOURIER) and were eligible for a long-term open-label extension. The objective of this current study was to assess the long-term effect of evolocumab on cognitive function. Cognitive function was assessed annually, and the primary end point was change from baseline in executive function within each group, measured using the spatial working memory strategy index score (range, 4-28), with lower scores indicating better performance.
Results
A total of 473 patients out of the 1974 patients in the parent EBBINGHAUS study were enrolled and additionally followed for a median of 5.1 years (maximum follow-up since original random assignment 7.2 years). The median age was 62 years; 70% were male, and 91% were White. At 12 weeks into the open-label extension period, median LDL cholesterol across the overall population was 35 mg/dl (interquartile range, 21-55 mg/dl). Treatment with evolocumab was not associated with a change in executive function during the open-label extension in either patients who were originally randomly assigned to and continued evolocumab (mean±standard deviation of 0.1±2.8, P=0.49) or patients originally randomly assigned to placebo who then started on evolocumab (-0.1±2.5, P=0.64). At the final study visit, executive function scores were similar between randomly assigned groups (17.5±3.7 and 17.3±3.7, respectively).
Conclusions
Exposure to very low levels of LDL cholesterol, achieved via PCSK9 inhibition and statin therapy, was not associated with cognitive impairment through long-term follow-up. Further studies are needed to assess the generalizability to adults at higher risk of dementia.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial.
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