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Updated: Jun 22, 2025

Evaluation of the Cognitive Performance of Hypertensive Patients with Silent Cerebrovascular Lesions
Published on: April 23, 2021
Sacubitril/Valsartan and Cognitive Outcomes in Heart Failure With Reduced Ejection Fraction
Prabhjot K Grewal1, Alan Abboud2, Evangelos Pavlos Myserlis3
1Department of Medicine, Stony Brook University, Stony Brook, New York, USA.
Background:
Recent trial data refute concerns about neurocognitive off-target effects of neprilysin inhibition with sacubitril and suggest benefit in patients with heart failure and ejection fraction >40%. We hypothesized that sacubitril/valsartan is associated with improved cognitive outcomes in patients with heart failure and reduced ejection fraction (HFrEF).
Objectives:
The purpose of this study was to compare 3-year cognitive outcomes in patients with HFrEF who receive sacubitril/valsartan vs angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs).
Methods:
Retrospective cohort study of: 1) 11,313 adults with HFrEF (International Classification of Diseases-10th Revision-Clinical Modification [ICD-10-CM] codes: I50.2 or I50.4) started on sacubitril/valsartan between 1/1/2015 and 12/31/2019; and 2) 11,313 propensity matched patients receiving ACEI/ARB during that time. Data were obtained from the TriNetX Research Network, encompassing 41 health care organizations in the United States. Primary endpoint was the composite of cognitive decline (ICD-10-CM: R41.8), dementia (ICD-10-CM: F01-F03), and Alzheimer's disease (ICD-10-CM: G30).
Results:
At 3 years, 858 patients on sacubitril/valsartan met the primary endpoint vs 1,209 on ACEI/ARB (3-year incidence: 10.7% vs 15.0%; HR: 0.69; 95% CI: 0.63-0.75; P < 0.001), with consistently lower rates of cognitive decline (9.5% vs 13.3%; HR: 0.69; 95% CI: 0.63-0.76; P < 0.001), dementia (3.4% vs 5.0%; HR: 0.65; 95% CI: 0.57-0.77; P < 0.001), and Alzheimer's disease (0.6% vs 1.3%; HR: 0.48; 95% CI: 0.35-0.66; P < 0.001) in the sacubitril/valsartan cohort. Results were consistent in matched sex and race subgroups. Three-year mortality was 22.0% on sacubitril/valsartan vs 24.6% on ACEI/ARB (HR: 0.89; 95% CI: 0.84-0.94; P < 0.001).
Conclusions:
Sacubitril/valsartan was associated with lower 3-year rates of neurocognitive disorders when compared to ACEI/ARBs in patients with HFrEF.
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