Effect of Sacubitril/Valsartan on Cognitive Function in Patients With Heart Failure With Preserved Ejection Fraction: A Prespecified Analysis of PARAGON-HF-Reference-Cited by-同舟云学术

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

Published:2024-07-23 Issue:4 Volume:150 Page:272-282
ISSN:0009-7322
Container-title:Circulation
language:en
Short-container-title:Circulation

Author:

Dewan Pooja¹,Shen Li¹²,Pedro Ferreira João³⁴,Jhund Pardeep S.¹^ORCID,Anand Inder S.⁵,Chandra Alvin⁶^ORCID,Chiang Lu-May⁷,Claggett Brian⁸^ORCID,Desai Akshay S.⁸^ORCID,Gong Jianjian⁷,Lam Carolyn S.P.⁹^ORCID,Lefkowitz Martin P.⁷^ORCID,Maggioni Aldo P.¹⁰^ORCID,Martinez Felipe¹¹^ORCID,Packer Milton¹²^ORCID,Redfield Margaret M.¹³^ORCID,Rouleau Jean L.¹⁴^ORCID,van Veldhuisen Dirk J.¹⁵^ORCID,Zannad Faiez³^ORCID,Zile Michael R.¹⁶¹⁷^ORCID,Solomon Scott D.⁸^ORCID,McMurray John J.V.¹

Affiliation:

1. BHF Cardiovascular Research Centre, University of Glasgow, UK (P.D., L.S., P.S.J., J.J.V.M.).

2. School of Clinical Medicine, Hangzhou Normal University, China (L.S.).

3. Centre d’Investigations Cliniques Plurithématique 1433 and Inserm U1116, CHRU Nancy, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), France (J.P.F., F.Z.).

4. Cardiovascular Research and Development Center, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Portugal (J.P.F.).

5. VA Medical Center, University of Minnesota, Minneapolis (I.S.A.).

6. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas (A.C.).

7. Novartis Pharmaceuticals, East Hanover, NJ (L.-M.C., J.G., M.P.L.).

8. Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, MA (B.C., A.S.D., S.D.S.).

9. National Heart Centre Singapore and Duke-National University of Singapore (C.S.P.L.).

10. National Association of Hospital Cardiologists Research Centre, Florence, Italy (A.P.M.).

11. National University of Cordoba, Argentina (F.M.).

12. Baylor Heart and Vascular Institute, Baylor University Medical Centre, Dallas, TX (M.P.).

13. Mayo Clinic, Rochester, MN (M.M.R.).

14. Institut de Cardiologie de Montreal, Universite de Montreal, Quebec, Canada (J.L.R.).

15. Department of Cardiology, University Medical Centre Groningen, University of Groningen, the Netherlands (D.J.v.V.).

16. Medical University of South Carolina, Charleston (M.R.Z.).

17. Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC (M.R.Z.).

Abstract

BACKGROUND: A hypothetical concern has been raised that sacubitril/valsartan might cause cognitive impairment because neprilysin is one of several enzymes degrading amyloid-β 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 ε4 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. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01920711.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Reference45 articles.

1. Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure

2. Amyloid-β in Alzheimer’s disease – front and centre after all?

3. Current status of amyloid-targeting immunotherapies for Alzheimer’s disease

4. Amyloid Beta in Aging and Alzheimer’s Disease

5. Neprilysin Inhibitors in Heart Failure