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Dementia-related adverse events in PARADIGM-HF and other trials in heart failure with reduced ejection fraction.
- Source :
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European journal of heart failure [Eur J Heart Fail] 2017 Jan; Vol. 19 (1), pp. 129-137. Date of Electronic Publication: 2016 Nov 20. - Publication Year :
- 2017
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Abstract
- Aims: 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.<br />Methods and Results: 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.<br />Conclusion: 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.<br /> (© 2016 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)
- Subjects :
- Aged
Amnesia epidemiology
Biphenyl Compounds
Confusion epidemiology
Delirium epidemiology
Disorders of Excessive Somnolence epidemiology
Drug Combinations
Female
Heart Failure physiopathology
Humans
Male
Middle Aged
Neprilysin antagonists & inhibitors
Proportional Hazards Models
Stroke Volume
Valsartan
Aminobutyrates therapeutic use
Angiotensin Receptor Antagonists therapeutic use
Angiotensin-Converting Enzyme Inhibitors therapeutic use
Dementia epidemiology
Enalapril therapeutic use
Heart Failure drug therapy
Tetrazoles therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0844
- Volume :
- 19
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- European journal of heart failure
- Publication Type :
- Academic Journal
- Accession number :
- 27868321
- Full Text :
- https://doi.org/10.1002/ejhf.687