1. Effect of sacubitril/valsartan on investigator-reported ventricular arrhythmias in PARADIGM-HF.
- Author
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Curtain, James P., Jackson, Alice M., Li Shen, Jhund, Pardeep S., Docherty, Kieran F., Petrie, Mark C., Castagno, Davide, Desai, Akshay S., Rohde, Luis E., Lefkowitz, Martin P., Rouleau, Jean-Lucien, Zile, Michael R., Solomon, Scott D., Swedberg, Karl, Packer, Milton, and McMurray, John J. V.
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STATISTICS , *CONFIDENCE intervals , *ENALAPRIL , *DISEASE incidence , *IMPLANTABLE cardioverter-defibrillators , *PROTEOLYTIC enzymes , *PARADIGMS (Social sciences) , *CARDIAC pacing , *COMPARATIVE studies , *RANDOMIZED controlled trials , *VENTRICULAR arrhythmia , *VALSARTAN , *CARDIAC arrest , *DATA analysis , *STATISTICAL sampling - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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