Effect of Sacubitril/Valsartan on Cognitive Function in Patients With Heart Failure With Preserved Ejection Fraction: A Prespecified Analysis of PARAGON-HF

Data de publicação: 01/01/2024

Autores da FMUP

João Pedro Melo Marques Pinho Ferreira

Autor

Participantes de fora da FMUP

Dewan P.
Shen L.
Jhund P.S.
Anand I.S.
Chandra A.
Chiang L.-M.
Claggett B.
Desai A.S.
Gong J.
Lam C.S.P.
Lefkowitz M.P.
Maggioni A.P.
Martinez F.
Packer M.
Redfield M.M.
Rouleau J.L.
van Veldhuisen D.J.
Zannad F.
Zile M.R.
Solomon S.D.
McMurray J.J.V.

Unidades de investigação

Abstract

BACKGROUND: A hypothetical concern has been raised that sacubitril/valsartan might cause cognitive impairment because neprilysin is one of several enzymes degrading amyloid-ß peptides in the brain, some of which are neurotoxic and linked to Alzheimer-type dementia. To address this, we examined the effect of sacubitril/valsartan compared with valsartan on cognitive function in patients with heart failure with preserved ejection fraction in a prespecified substudy of PARAGON-HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction). METHODS: In PARAGON-HF, serial assessment of cognitive function was conducted in a subset of patients with the Mini-Mental State Examination (MMSE; score range, 0-30, with lower scores reflecting worse cognitive function). The prespecified primary analysis of this substudy was the change from baseline in MMSE score at 96 weeks. Other post hoc analyses included cognitive decline (fall in MMSE score of =3 points), cognitive impairment (MMSE score <24), or the occurrence of dementia-related adverse events. RESULTS: Among 2895 patients included in the MMSE substudy with baseline MMSE score measured, 1453 patients were assigned to sacubitril/valsartan and 1442 to valsartan. Their mean age was 73 years, and the median follow-up was 32 months. The mean±SD MMSE score at randomization was 27.4±3.0 in the sacubitril/valsartan group, with 10% having an MMSE score <24; the corresponding numbers were nearly identical in the valsartan group. The mean change from baseline to 96 weeks in the sacubitril/valsartan group was -0.05 (SE, 0.07); the corresponding change in the valsartan group was -0.04 (0.07). The mean between-treatment difference at week 96 was -0.01 (95% CI, -0.20 to 0.19; P=0.95). Analyses of a =3-point decline in MMSE, decrease to a score <24, dementia-related adverse events, and combinations of these showed no difference between sacubitril/valsartan and valsartan. No difference was found in the subgroup of patients tested for apolipoprotein E e4 allele genotype. CONCLUSIONS: Patients with heart failure with preserved ejection fraction in PARAGON-HF had relatively low baseline MMSE scores. Cognitive change, measured by MMSE, did not differ between treatment with sacubitril/valsartan and treatment with valsartan in patients with heart failure with preserved ejection fraction. © 2024 American Heart Association, Inc.

Dados da publicação

ISSN/ISSNe:: 0009-7322, 1524-4539
Tipo:: Article
Páginas:: 272-282
DOI:: 10.1161/CIRCULATIONAHA.124.068774
Link para outro recurso:: www.scopus.com

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Keywords

Aged; Aged, 80 and over; Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Cognition; Cognitive Dysfunction; Drug Combinations; Female; Heart Failure; Humans; Male; Middle Aged; Neprilysin; Prospective Studies; Stroke Volume; Tetrazoles; Treatment Outcome; Valsartan; amyloid beta protein; apolipoprotein E; enalapril; sacubitril; valsartan; aminobutyric acid derivative; angiotensin receptor antagonist; biphenyl derivative; membrane metalloendopeptidase; sacubitril and valsartan sodium hydrate drug combination; tetrazole derivative; valsartan; adult; aged; Alzheimer disease; angioneurotic edema; Article; body mass; cardiovascular disease; cognition; cognitive defect; controlled study; coronary atherosclerosis; delirium; dementia; depression; estimated glomerular filtration rate; female; follow up; genotype; glomerulus filtration rate; heart ejection fraction; heart failure; heart failure with preserved ejection fraction; heart failure with reduced ejection fraction; h