Sacubitril/valsartan and the risk of incident dementia in heart failure: a nationwide propensity-matched cohort study

Lee, Hyun-Jung; Kim, Hyung-Kwan; Kim, Bong-Seong; Han, Kyung-Do; Kwak, Soongu; Park, Chan Soon; Rhee, Tae-Min; Park, Jun-Bean; Lee, Heesun; Kim, Yong-Jin

doi:10.1007/s00392-023-02322-0

Cited by 3 publications

(2 citation statements)

References 25 publications

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“…13 Several recent postmarketing community surveys have also shown no suggestion of increased cognitive AEs with sacubitril/valsartan. [37][38][39][40] Collectively, these findings do not support the hypothetical concern that neprilysin inhibition might accelerate cognitive decline in patients with heart failure. [5][6][7][8][9] This view is also consistent with the finding that sacubitril/valsartan did not increase the concentration of amyloidogenic species in the cerebrospinal fluid of healthy volunteers or brain tissue in cynomolgus monkeys and the evidence that multiple other pathways are also responsible for the clearance of neurotoxic Aβ peptides from the central nervous system.…”

Section: Dementia During Follow-upmentioning

confidence: 61%

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

Dewan,

Shen,

Pedro Ferreira

et al. 2024

Circulation

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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 MMSEs 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.

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Section: Dementia During Follow-upmentioning

confidence: 61%

“…13 Several recent postmarketing community surveys have also shown no suggestion of increased cognitive AEs with sacubitril/valsartan. 37–40…”

Section: Discussionmentioning

confidence: 99%

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

Dewan,

Shen,

Pedro Ferreira

et al. 2024

Circulation

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Clinical and serological characterization of acute pleuropericarditis suggests an autoinflammatory pathogenesis and highlights risk factors for recurrent attacks

Kaudewitz,

John,

Meis

et al. 2024

Clin Res Cardiol

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Purpose We describe the manifestations and course of patients with pleuropericarditis (PP). Serum parameters were analyzed to evaluate the contribution of autoimmune and autoinflammatory mechanisms to PP pathogenesis. Finally, we outline risk factors for recurrent PP attacks. Methods Electronic medical records of the University Hospital Heidelberg were screened for PP diagnosis between the years 2009 and 2021. A total of 164 patients were detected and compared to patients suffering from systemic lupus erythematosus (SLE)-associated PP. Follow-up data were collected until January 2023. Results In 57.3% of a total of 164 PP cases, no trigger was identified (idiopathic PP). The clinical manifestations were similar in subgroups with different triggers (idiopathic, post-cardiac injury and post-infectious). None of the patients in the idiopathic-PP (i-PP) group fulfilled the diagnostic criteria of an autoimmune disease and the i-PP group could be clearly discriminated by clinical, epidemiological and serological means from the control cohort of SLE-associated PP. After a median follow-up of 1048 days, the majority of PP patients (72.7%) had at least one PP relapse. Univariate analyses showed that CRP, SAA (serum amyloid A), troponin T, NT-BNP and post-cardiac injury were negatively correlated, while the presence of fever and an idiopathic trigger were positively correlated with recurrence of PP. Multivariate analyses showed that fever, an idiopathic trigger and low SAA values were risk factors for PP recurrence. Conclusion This study highlights that most cases of PP are idiopathic and PP cases with various triggers have an identical clinical phenotype. Our data suggest that the clinical, epidemiological and serological characteristics of idiopathic PP considerably differ from patients with PP caused by autoimmune disease like SLE. We further demonstrate that PP has a high risk of recurrence and identify factors associated with this risk, allowing for a targeted secondary prophylaxis. Graphical Abstract

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Association between treatment with sacubitril/valsartan and the risk of Alzheimer’s disease: a clinical update

Garnier-Crussard

2024

Alz Res Therapy

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Since 2014, sacubitril/valsartan (Entresto®) is widely prescribed for heart failure. Despite neprilysin inhibition’s benefits in heart failure, concerns about potential amyloid-beta (Aβ) accumulation and Alzheimer’s disease (AD) risk have persisted. This narrative review, a decade post-approval, evaluates the risk of amyloid pathology and neurocognitive disorders in long-term sacubitril/valsartan use. Clinical trials, real-world studies, and pharmacovigilance data do not indicate an increased risk of cognitive decline. In patients treated with sacubitril/valsartan blood-based amyloid biomarkers show perturbations, while neuroimaging biomarkers reveal no significant increase in amyloid load. Despite a theoretical risk of amyloid accumulation and AD under treatment with sacubitril/valsartan, current clinical data appears reassuring, and there is no signal indicating an increased risk of cognitive decline, but a perturbation of amyloid blood-based biomarkers, which implies great caution when interpreting biomarkers in this context.

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Sacubitril/valsartan and the risk of incident dementia in heart failure: a nationwide propensity-matched cohort study

Cited by 3 publications

References 25 publications

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

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

Clinical and serological characterization of acute pleuropericarditis suggests an autoinflammatory pathogenesis and highlights risk factors for recurrent attacks

Association between treatment with sacubitril/valsartan and the risk of Alzheimer’s disease: a clinical update

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