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Novel concept to guide systolic heart failure medication by repeated biomarker testing—results from TIME-CHF in context of predictive, preventive, and personalized medicine
BACKGROUND: It is uncertain whether repeated measurements of a multi-target biomarker panel may help to personalize medical heart failure (HF) therapy to improve outcome in chronic HF. METHODS: This analysis included 499 patients from the Trial of Intensified versus standard Medical therapy in Elder...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972133/ https://www.ncbi.nlm.nih.gov/pubmed/29896315 http://dx.doi.org/10.1007/s13167-018-0137-7 |
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author | Davarzani, Nasser Sanders-van Wijk, Sandra Maeder, Micha T. Rickenbacher, Peter Smirnov, Evgueni Karel, Joël Suter, Thomas de Boer, Rudolf A. Block, Dirk Rolny, Vinzent Zaugg, Christian Pfisterer, Matthias E. Peeters, Ralf Brunner-La Rocca, Hans-Peter |
author_facet | Davarzani, Nasser Sanders-van Wijk, Sandra Maeder, Micha T. Rickenbacher, Peter Smirnov, Evgueni Karel, Joël Suter, Thomas de Boer, Rudolf A. Block, Dirk Rolny, Vinzent Zaugg, Christian Pfisterer, Matthias E. Peeters, Ralf Brunner-La Rocca, Hans-Peter |
author_sort | Davarzani, Nasser |
collection | PubMed |
description | BACKGROUND: It is uncertain whether repeated measurements of a multi-target biomarker panel may help to personalize medical heart failure (HF) therapy to improve outcome in chronic HF. METHODS: This analysis included 499 patients from the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF), aged ≥ 60 years, LVEF ≤ 45%, and NYHA ≥ II, who had repeated clinical visits within 19 months follow-up. The interaction between repeated measurements of biomarkers and treatment effects of loop diuretics, spironolactone, β-blockers, and renin-angiotensin system (RAS) inhibitors on risk of HF hospitalization or death was investigated in a hypothesis-generating analysis. Generalized estimating equation (GEE) models were used to account for the correlation between recurrences of events in a patient. RESULTS: One hundred patients (20%) had just one event (HF hospitalization or death) and 87 (17.4%) had at least two events. Loop diuretic up-titration had a beneficial effect for patients with high interleukin-6 (IL6) or high high-sensitivity C-reactive protein (hsCRP) (interaction, P = 0.013 and P = 0.001), whereas the opposite was the case with low hsCRP (interaction, P = 0.013). Higher dosage of loop diuretics was associated with poor outcome in patients with high blood urea nitrogen (BUN) or prealbumin (interaction, P = 0.006 and P = 0.001), but not in those with low levels of these biomarkers. Spironolactone up-titration was associated with lower risk of HF hospitalization or death in patients with high cystatin C (CysC) (interaction, P = 0.021). β-Blockers up-titration might have a beneficial effect in patients with low soluble fms-like tyrosine kinase-1 (sFlt) (interaction, P = 0.021). No treatment biomarker interactions were found for RAS inhibition. CONCLUSION: The data of this post hoc analysis suggest that decision-making using repeated biomarker measurements may be very promising in bringing treatment of heart failure to a new level in the context of predictive, preventive, and personalized medicine. Clearly, prospective testing is needed before this novel concept can be adopted. CLINICAL TRIAL REGISTRATION: isrctn.org, identifier: ISRCTN43596477 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13167-018-0137-7) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5972133 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-59721332018-06-12 Novel concept to guide systolic heart failure medication by repeated biomarker testing—results from TIME-CHF in context of predictive, preventive, and personalized medicine Davarzani, Nasser Sanders-van Wijk, Sandra Maeder, Micha T. Rickenbacher, Peter Smirnov, Evgueni Karel, Joël Suter, Thomas de Boer, Rudolf A. Block, Dirk Rolny, Vinzent Zaugg, Christian Pfisterer, Matthias E. Peeters, Ralf Brunner-La Rocca, Hans-Peter EPMA J Research BACKGROUND: It is uncertain whether repeated measurements of a multi-target biomarker panel may help to personalize medical heart failure (HF) therapy to improve outcome in chronic HF. METHODS: This analysis included 499 patients from the Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF), aged ≥ 60 years, LVEF ≤ 45%, and NYHA ≥ II, who had repeated clinical visits within 19 months follow-up. The interaction between repeated measurements of biomarkers and treatment effects of loop diuretics, spironolactone, β-blockers, and renin-angiotensin system (RAS) inhibitors on risk of HF hospitalization or death was investigated in a hypothesis-generating analysis. Generalized estimating equation (GEE) models were used to account for the correlation between recurrences of events in a patient. RESULTS: One hundred patients (20%) had just one event (HF hospitalization or death) and 87 (17.4%) had at least two events. Loop diuretic up-titration had a beneficial effect for patients with high interleukin-6 (IL6) or high high-sensitivity C-reactive protein (hsCRP) (interaction, P = 0.013 and P = 0.001), whereas the opposite was the case with low hsCRP (interaction, P = 0.013). Higher dosage of loop diuretics was associated with poor outcome in patients with high blood urea nitrogen (BUN) or prealbumin (interaction, P = 0.006 and P = 0.001), but not in those with low levels of these biomarkers. Spironolactone up-titration was associated with lower risk of HF hospitalization or death in patients with high cystatin C (CysC) (interaction, P = 0.021). β-Blockers up-titration might have a beneficial effect in patients with low soluble fms-like tyrosine kinase-1 (sFlt) (interaction, P = 0.021). No treatment biomarker interactions were found for RAS inhibition. CONCLUSION: The data of this post hoc analysis suggest that decision-making using repeated biomarker measurements may be very promising in bringing treatment of heart failure to a new level in the context of predictive, preventive, and personalized medicine. Clearly, prospective testing is needed before this novel concept can be adopted. CLINICAL TRIAL REGISTRATION: isrctn.org, identifier: ISRCTN43596477 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13167-018-0137-7) contains supplementary material, which is available to authorized users. Springer International Publishing 2018-05-13 /pmc/articles/PMC5972133/ /pubmed/29896315 http://dx.doi.org/10.1007/s13167-018-0137-7 Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Research Davarzani, Nasser Sanders-van Wijk, Sandra Maeder, Micha T. Rickenbacher, Peter Smirnov, Evgueni Karel, Joël Suter, Thomas de Boer, Rudolf A. Block, Dirk Rolny, Vinzent Zaugg, Christian Pfisterer, Matthias E. Peeters, Ralf Brunner-La Rocca, Hans-Peter Novel concept to guide systolic heart failure medication by repeated biomarker testing—results from TIME-CHF in context of predictive, preventive, and personalized medicine |
title | Novel concept to guide systolic heart failure medication by repeated biomarker testing—results from TIME-CHF in context of predictive, preventive, and personalized medicine |
title_full | Novel concept to guide systolic heart failure medication by repeated biomarker testing—results from TIME-CHF in context of predictive, preventive, and personalized medicine |
title_fullStr | Novel concept to guide systolic heart failure medication by repeated biomarker testing—results from TIME-CHF in context of predictive, preventive, and personalized medicine |
title_full_unstemmed | Novel concept to guide systolic heart failure medication by repeated biomarker testing—results from TIME-CHF in context of predictive, preventive, and personalized medicine |
title_short | Novel concept to guide systolic heart failure medication by repeated biomarker testing—results from TIME-CHF in context of predictive, preventive, and personalized medicine |
title_sort | novel concept to guide systolic heart failure medication by repeated biomarker testing—results from time-chf in context of predictive, preventive, and personalized medicine |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972133/ https://www.ncbi.nlm.nih.gov/pubmed/29896315 http://dx.doi.org/10.1007/s13167-018-0137-7 |
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