Because neprilysin is involved in the degradation of amyloid-beta, there is concern that the angiotensin-neprilysin inhibitor Sacubitril - Valsartan ( Entresto ) could increase the risk for dementia.
Researchers have analyzed adverse event cases submitted to the Food and Drug Administration Adverse Event Report System ( FAERS ) from July 2015 to March 2017.
Cognition- and dementia-related adverse event cases were defined with the use of broad and narrow structured medical queries.
During the period evaluated, 9,004 adverse event reports ( out of a total of 2,249,479 ) involved the use of combination Sacubitril and Valsartan.
Based on the broad definition, combination of Sacubitril and Valsartan was associated with cognition- and dementia-related adverse events in 459 reports ( 5.1% ), but this was lower than the proportion of these reports among other medications ( 6.6%, reporting odds ratio [ ROR ] 0.72, 95% confidence interval [ CI ] 0.65-0.79 ).
Restricting the comparison to cases with age more than 60 years and with the use of a comparator group with heart failure resulted in no association between Sacubitril and valsartan and dementia-related adverse events, with the use of both the broad and the narrow definitions ( ROR 0.87, 95% CI 0.76-1.02, and ROR 1.06, 95% CI 0.4-3.16, respectively ).
In conclusion, Sacubitril-Valsartan is not associated with a disproportionately high rate of short-term dementia-related adverse effect reports.
Long-term studies assessing cognitive outcomes are required to better establish the medication's cognition effects. ( Xagena )
Perlman A et al, J Card Fail 2018; 24: 533-536