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

Aims 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 i...

Full description

Bibliographic Details
Authors: Curtain, James P., Jackson, Alice M., Shen, Li, Jhund, Pardeep S., Docherty, Kieran F., Petrie, Mark C., Castagno, Davide, Desai, Akshay S., Rohde, Luis Eduardo Paim, Lefkowitz, Martin, Rouleau, Jean, Zile, Michael R., Solomon, Scott D., Swedberg, Karl, Packer, Milton, McMurray, John J. V.
Format: article
Status:Published version
Publication Date:2022
Country:Brasil
Institution:Universidade Federal do Rio Grande do Sul (UFRGS)
Repository:Repositório Institucional da UFRGS
Language:English
OAI Identifier:oai:www.lume.ufrgs.br:10183/267158
Online Access:http://hdl.handle.net/10183/267158
Access Level:Open access
Keyword:Insuficiência cardíaca
Neprilisina
Taquicardia ventricular
Neprilysin inhibitor
Heart failure
Ventricular tachyarrhythmia
Description
Summary:Aims 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. Methods and results 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). 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.

Similar Items