Effect of sacubitril/valsartan on investigator-reported ventricular arrhythmias in PARADIGM-HF

Curtain, J. P. et al. (2022) Effect of sacubitril/valsartan on investigator-reported ventricular arrhythmias in PARADIGM-HF. European Journal of Heart Failure, 24(3), pp. 551-561. (doi: 10.1002/ejhf.2419) (PMID:34969175)

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Background: Sudden death is a leading cause of mortality in HFrEF. In PARADIGM-HF, sacubitril/valsartan reduced the incidence of sudden death. The purpose of this post hoc study was to analyze the effect of sacubitril/valsartan, compared to enalapril, on the incidence of ventricular arrhythmias. Methods: Adverse event reports related to ventricular arrhythmias were examined in PARADIGM-HF. The effect of randomized treatment on two arrhythmia outcomes was analyzed: ventricular arrhythmias and the composite of a ventricular arrhythmia, 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/CRT-D use, and the effect of sacubitril/valsartan was analyzed. Results: 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 [HR 0.76 (0.62–0.95); p = 0.015] and the composite arrhythmia outcome [HR 0.79 (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 effect of sacubitril/valsartan, but aetiology did: HR in patients with an ischaemic aetiology 0.93 (0.71–1.21) versus 0.53 (0.37–0.78) in those without an ischaemic aetiology (p for interaction = 0.020). Conclusions: 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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Docherty, Dr Kieran and Shen, Dr Li and Petrie, Professor Mark and McMurray, Professor John and Jackson, Dr Alice and Curtain, Dr James and Jhund, Professor Pardeep
Authors: Curtain, J. P., Jackson, A., Shen, L., Jhund, P. S., Docherty, K. F., Petrie, M. C., Castagno, D., Desai, A. S., Rohde, L. E., Lefkowitz, M. P., Rouleau, J.-L., Zile, M. R., Solomon, S. D., Swedberg, K., Packer, M., and McMurray, J. J.V.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:European Journal of Heart Failure
ISSN (Online):1879-0844
Published Online:30 December 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in European Journal of Heart Failure 24(3): 551-561
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303944BHF Centre of ExcellenceColin BerryBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science
301144The epidemiology of peripartum cardiomyopathy in a Western European country: An analysis of the Scottish population 1990-2016Pardeep JhundBritish Heart Foundation (BHF)FS/18/14/33330Institute of Cardiovascular & Medical Sciences