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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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Ltd.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9542658/ https://www.ncbi.nlm.nih.gov/pubmed/34969175 http://dx.doi.org/10.1002/ejhf.2419 |
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author | Curtain, James P. Jackson, Alice M. Shen, Li 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 McMurray, John J.V. |
author_facet | Curtain, James P. Jackson, Alice M. Shen, Li 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 McMurray, John J.V. |
author_sort | Curtain, James P. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9542658 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley & Sons, Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95426582022-10-14 Effect of sacubitril/valsartan on investigator‐reported ventricular arrhythmias in PARADIGM‐HF Curtain, James P. Jackson, Alice M. Shen, Li 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 McMurray, John J.V. Eur J Heart Fail Medical Therapy 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. John Wiley & Sons, Ltd. 2022-01-19 2022-03 /pmc/articles/PMC9542658/ /pubmed/34969175 http://dx.doi.org/10.1002/ejhf.2419 Text en © 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Medical Therapy Curtain, James P. Jackson, Alice M. Shen, Li 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 McMurray, John J.V. Effect of sacubitril/valsartan on investigator‐reported ventricular arrhythmias in PARADIGM‐HF |
title | Effect of sacubitril/valsartan on investigator‐reported ventricular arrhythmias in PARADIGM‐HF
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title_full | Effect of sacubitril/valsartan on investigator‐reported ventricular arrhythmias in PARADIGM‐HF
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title_fullStr | Effect of sacubitril/valsartan on investigator‐reported ventricular arrhythmias in PARADIGM‐HF
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title_full_unstemmed | Effect of sacubitril/valsartan on investigator‐reported ventricular arrhythmias in PARADIGM‐HF
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title_short | Effect of sacubitril/valsartan on investigator‐reported ventricular arrhythmias in PARADIGM‐HF
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title_sort | effect of sacubitril/valsartan on investigator‐reported ventricular arrhythmias in paradigm‐hf |
topic | Medical Therapy |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9542658/ https://www.ncbi.nlm.nih.gov/pubmed/34969175 http://dx.doi.org/10.1002/ejhf.2419 |
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