Effect of sacubitril/valsartan on investigator-reported ventricular arrhythmias in PARADIGM-HF.
Heart failure
Neprilysin inhibitor
Ventricular tachyarrhythmia
Journal
European journal of heart failure
ISSN: 1879-0844
Titre abrégé: Eur J Heart Fail
Pays: England
ID NLM: 100887595
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
revised:
17
12
2021
received:
08
09
2021
accepted:
23
12
2021
pubmed:
31
12
2021
medline:
8
4
2022
entrez:
30
12
2021
Statut:
ppublish
Résumé
Sudden death is a leading cause of mortality in heart failure with reduced ejection fraction (HFrEF). In PARADIGM-HF, sacubitril/valsartan reduced the incidence of sudden death. The purpose of this post hoc study was to analyse the effect of sacubitril/valsartan, compared to enalapril, on the incidence of ventricular arrhythmias. Adverse event reports related to ventricular arrhythmias were examined in PARADIGM-HF. The effect of randomized treatment on two arrhythmia outcomes was analysed: ventricular arrhythmias and the composite of a ventricular arrhythmia, implantable cardioverter defibrillator (ICD) shock or resuscitated cardiac arrest. The risk of death related to a ventricular arrhythmia was examined in time-updated models. The interaction between heart failure aetiology, or baseline ICD/cardiac resynchronization therapy-defibrillator (CRT-D) use, and the effect of sacubitril/valsartan was analysed. Of the 8399 participants, 333 (4.0%) reported a ventricular arrhythmia and 372 (4.4%) the composite arrhythmia outcome. Ventricular arrhythmias were associated with higher mortality. Compared with enalapril, sacubitril/valsartan reduced the risk of a ventricular arrhythmia (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.62-0.95; p = 0.015) and the composite arrhythmia outcome (HR 0.79, 95% CI 0.65-0.97; p = 0.025). The treatment effect was maintained after adjustment and accounting for the competing risk of death. Baseline ICD/CRT-D use did not modify the effect of sacubitril/valsartan, but aetiology did: HR in patients with an ischaemic aetiology 0.93 (95% CI 0.71-1.21) versus 0.53 (95% CI 0.37-0.78) in those without an ischaemic aetiology (p for interaction = 0.020). Sacubitril/valsartan reduced the incidence of investigator-reported ventricular arrhythmias in patients with HFrEF. This effect may have been greater in patients with a non-ischaemic aetiology.
Identifiants
pubmed: 34969175
doi: 10.1002/ejhf.2419
pmc: PMC9542658
doi:
Substances chimiques
Aminobutyrates
0
Angiotensin Receptor Antagonists
0
Biphenyl Compounds
0
Drug Combinations
0
Tetrazoles
0
sacubitril
17ERJ0MKGI
Valsartan
80M03YXJ7I
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
551-561Subventions
Organisme : British Heart Foundation
ID : RE/18/6/34217
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/18/14/33330
Pays : United Kingdom
Informations de copyright
© 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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