ESC 2022: Are neprilysin inhibitors safe for cognitive function in patients with chronic HF?

ESC 2022: Are neprilysin inhibitors safe for cognitive function in patients with chronic HF?

Cognitive decline and dementia are common in patients with heart failure (HF), impacting quality of life, medication adherence, and cardiovascular outcomes. Some studies suggest that neprilysin inhibitor sacubritril may worsen this cognitive decline, as it is one of the enzymes involved in the degradation of beta-amyloid peptides. This degradation could lead to the accumulation of a neurotoxic peptide, which causes dementia, with consequent cognitive deterioration in the patient with HF. On the contrary, treating HF with medication could protect the patient from dementia by improving cerebral flow.

Based on this, a study, called PERSPECTIVE, presented at the ESC 2022 congress, was carried out to evaluate the efficacy and safety of sacubitril/valsartan on the cognitive function of patients with chronic heart failure (HF) and preserved ejection fraction.

The study

It was a global, prospective, randomized, blinded study that compared 592 patients with HF regarding the use of sacubitril/valsartan or valsartan at a mean follow-up of three years. Patients with Alzheimer’s or other dementias were excluded.

Patients were serially evaluated for cognitive function with the CogState tests, which consist of the assessment of seven tasks that analyze three main cognitive domains. This was the primary outcome. The deposition of amyloid beta peptides in the brain was evaluated using positron emission tomography (PET) and the changes found in this exam were the secondary outcome.

the age mIt isday was 72 years and patient characteristics and HF treatment were similar between groups. There was no difference regarding cognitive outcomes at baseline.

At the 3-year follow-up, there was no difference in the primary outcome and, interestingly, in the secondary outcome there was a trend (not statistically significant result) of lower accumulation of beta-amyloid peptides in the sacubitril/valsartan group.


Based on this study, there should be no concern about the safety of neprilysin inhibitor-related use. The cognition. However, the high prevalence of cognitive dysfunction, even if mild, in patients with HF is important and should ber investigated further. It is important to emphasize that patients with reduced ejection fraction were not evaluated, since these tandm indication of sacubitril/valsartan preferably over The valsartan.

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