PMID- 36971193
OWN - NLM
STAT- MEDLINE
DCOM- 20230807
LR  - 20230807
IS  - 1755-5949 (Electronic)
IS  - 1755-5930 (Print)
IS  - 1755-5930 (Linking)
VI  - 29
IP  - 9
DP  - 2023 Sep
TI  - Updated insights on dementia-related risk of sacubitril/valsartan: A real-world 
      pharmacovigilance analysis.
PG  - 2548-2554
LID - 10.1111/cns.14195 [doi]
AB  - AIM: Sacubitril/valsartan is a new cardiovascular agent characterized by its dual 
      inhibition on the reninangiotensin system (RAS) and the neprilysin. As neprilysin 
      also involved itself in the degradation of amyloid-beta, there is an ongoing concern 
      about the effect of sacubitril/valsartan on cognition, especially in case of 
      long-term administration. METHODS: The FDA Adverse Event Reporting System (FAERS) 
      was mined between 2015Q3 and 2022Q4 to analyze the association between 
      sacubitril/valsartan and adverse events (AEs) involving dementia. Standardized 
      Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) with "broad" 
      and "narrow" preferred terms (PTs) relevant to dementia was applied to 
      systematically search demented AE reports. The Empirical Bayes Geometric Mean 
      (EBGM) from Multi-Item Gamma Poisson Shrinker (MGPS) and proportional reporting 
      ratio with Chi-square (PRR, chi(2) ) were used to calculate the disproportionality. 
      RESULTS: We filtered the query for indication and identified 80,316 reports with 
      heart failure indication in FAERS during the analytical period. Among all the 
      reports, sacubitril/valsartan was listed as primary suspected or secondary 
      suspected drug in 29,269 cases. No significantly elevated reporting rates of 
      narrow dementia were evident with sacubitril/valsartan. The EBGM05 for narrow 
      dementia-related AEs associated with sacubitril/valsartan was 0.88 and the PRR 
      (chi(2) ) was 1.22 (2.40). Similarly, broad demented complications were not 
      over-reported in the heart failure patients administrated with 
      sacubitril/valsartan (EBGM05 1.11; PRR 1.31, chi(2) 109.36). CONCLUSION: The number 
      of dementia-related cases reported to FAERS generate no safety signal 
      attributable to sacubitril/valsartan in patients with heart failure for now. 
      Further follow-ups are still warranted to address this question.
CI  - (c) 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & 
      Sons Ltd.
FAU - Chen, Congqin
AU  - Chen C
AD  - Department of Pharmacy, Xiamen Cardiovascular Hospital of Xiamen University, 
      School of Medicine, Xiamen University, Xiamen, China.
FAU - Ding, Lingqing
AU  - Ding L
AD  - Department of Pharmacy, Xiamen Cardiovascular Hospital of Xiamen University, 
      School of Medicine, Xiamen University, Xiamen, China.
FAU - Fu, Fang
AU  - Fu F
AD  - Department of Pharmacy, Xiamen Cardiovascular Hospital of Xiamen University, 
      School of Medicine, Xiamen University, Xiamen, China.
FAU - Xiao, Jie
AU  - Xiao J
AUID- ORCID: 0000-0002-2871-4086
AD  - Department of Pharmacy, Xiamen Cardiovascular Hospital of Xiamen University, 
      School of Medicine, Xiamen University, Xiamen, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230327
PL  - England
TA  - CNS Neurosci Ther
JT  - CNS neuroscience & therapeutics
JID - 101473265
RN  - 17ERJ0MKGI (sacubitril)
RN  - 0 (Tetrazoles)
RN  - EC 3.4.24.11 (Neprilysin)
RN  - 0 (Angiotensin Receptor Antagonists)
RN  - 80M03YXJ7I (Valsartan)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Drug Combinations)
SB  - IM
MH  - Humans
MH  - Tetrazoles/adverse effects
MH  - Neprilysin
MH  - Pharmacovigilance
MH  - Bayes Theorem
MH  - Angiotensin Receptor Antagonists/adverse effects
MH  - Valsartan/adverse effects
MH  - *Heart Failure/drug therapy/epidemiology/chemically induced
MH  - Biphenyl Compounds/adverse effects
MH  - Drug Combinations
MH  - *Dementia/drug therapy/epidemiology
PMC - PMC10401082
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - FAERS
OT  - dementia
OT  - pharmacovigilance study
OT  - sacubitril/valsartan
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/03/28 06:00
MHDA- 2023/08/07 06:42
PMCR- 2023/03/27
CRDT- 2023/03/27 06:22
PHST- 2023/03/16 00:00 [revised]
PHST- 2022/11/25 00:00 [received]
PHST- 2023/03/17 00:00 [accepted]
PHST- 2023/08/07 06:42 [medline]
PHST- 2023/03/28 06:00 [pubmed]
PHST- 2023/03/27 06:22 [entrez]
PHST- 2023/03/27 00:00 [pmc-release]
AID - CNS14195 [pii]
AID - 10.1111/cns.14195 [doi]
PST - ppublish
SO  - CNS Neurosci Ther. 2023 Sep;29(9):2548-2554. doi: 10.1111/cns.14195. Epub 2023 
      Mar 27.