Unknown

Dataset Information

0

Dementia-related adverse events in PARADIGM-HF and other trials in heart failure with reduced ejection fraction.


ABSTRACT: Inhibition of neprilysin, an enzyme degrading natriuretic and other vasoactive peptides, is beneficial in heart failure with reduced ejection fraction (HFrEF), as shown in PARADIGM-HF which compared the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan with enalapril. As neprilysin is also one of many enzymes clearing amyloid-β peptides from the brain, there is a theoretical concern about the long-term effects of sacubitril/valsartan on cognition. Therefore, we have examined dementia-related adverse effects (AEs) in PARADIGM-HF and placed these findings in the context of other recently conducted HFrEF trials.In PARADIGM-HF, patients with symptomatic HFrEF were randomized to sacubitril/valsartan 97/103 mg b.i.d. or enalapril 10 mg b.i.d. in a 1:1 ratio. We systematically searched AE reports, coded using the Medical Dictionary for Regulatory Activities (MedDRA), using Standardized MedDRA Queries (SMQs) with 'broad' and 'narrow' preferred terms related to dementia. In PARADIGM-HF, 8399 patients aged 18-96 years were randomized and followed for a median of 2.25 years (up to 4.3 years). The narrow SMQ search identified 27 dementia-related AEs: 15 (0.36%) on enalapril and 12 (0.29%) on sacubitril/valsartan [hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.33-1.59]. The broad search identified 97 (2.30%) and 104 (2.48%) AEs (HR 1.01, 95% CI 0.75-1.37), respectively. The rates of dementia-related AEs in both treatment groups in PARADIGM-HF were similar to those in three other recent trials in HFrEF.We found no evidence that sacubitril/valsartan, compared with enalapril, increased dementia-related AEs, although longer follow-up may be necessary to detect such a signal and more sensitive tools are needed to detect lesser degrees of cognitive impairment. Further studies to address this question are warranted.

SUBMITTER: Cannon JA 

PROVIDER: S-EPMC5248626 | BioStudies | 2017-01-01

SECONDARY ACCESSION(S): NCT01920711

REPOSITORIES: biostudies

Similar Datasets

2019-01-01 | S-EPMC6554586 | BioStudies
2020-01-01 | S-EPMC6972579 | BioStudies
2017-01-01 | S-EPMC5634378 | BioStudies
2016-01-01 | S-EPMC5490929 | BioStudies
2016-01-01 | S-EPMC5013095 | BioStudies
2020-01-01 | S-EPMC7768573 | BioStudies
2016-01-01 | S-EPMC5253408 | BioStudies
2020-01-01 | S-EPMC7772612 | BioStudies
2017-01-01 | S-EPMC5645149 | BioStudies
2020-01-01 | S-EPMC7754944 | BioStudies