Novel concept to guide systolic heart failure medication by repeated biomarker testing—results from TIME-CHF in context of predictive, preventive, and personalized medicine

Nasser Davarzani, Sandra Sanders-van Wijk, Micha T. Maeder, Peter Rickenbacher, Evgueni Smirnov, Joël Karel, Thomas Suter, Rudolf A. de Boer, Dirk Block, Vinzent Rolny, Christian Zaugg, Matthias E. Pfisterer, Ralf Peeters, Hanspeter Brunner-La Rocca

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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 = 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, beta-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). beta-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.

Original languageEnglish
Pages (from-to)161-173
Number of pages13
JournalThe EPMA Journal
Volume9
Issue number2
DOIs
Publication statusPublished - Jun 2018

Keywords

  • Heart failure
  • Biomarker
  • Heart failure medication
  • Predictive preventive personalized medicine
  • Generalized estimating equations
  • LONGITUDINAL DATA-ANALYSIS
  • BLOOD UREA NITROGEN
  • NATRIURETIC PEPTIDE
  • ESTIMATING EQUATIONS
  • TYROSINE KINASE-1
  • DISEASE SEVERITY
  • ELDERLY-PATIENTS
  • THERAPY
  • MORTALITY
  • MANAGEMENT

Cite this

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, Hanspeter. / Novel concept to guide systolic heart failure medication by repeated biomarker testing—results from TIME-CHF in context of predictive, preventive, and personalized medicine. In: The EPMA Journal. 2018 ; Vol. 9, No. 2. pp. 161-173.
@article{341a8f00e8a14e8ea0cdd3e9c0417aea,
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",
abstract = "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 = 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, beta-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). beta-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.",
keywords = "Heart failure, Biomarker, Heart failure medication, Predictive preventive personalized medicine, Generalized estimating equations, LONGITUDINAL DATA-ANALYSIS, BLOOD UREA NITROGEN, NATRIURETIC PEPTIDE, ESTIMATING EQUATIONS, TYROSINE KINASE-1, DISEASE SEVERITY, ELDERLY-PATIENTS, THERAPY, MORTALITY, MANAGEMENT",
author = "Nasser Davarzani and {Sanders-van Wijk}, Sandra and Maeder, {Micha T.} and Peter Rickenbacher and Evgueni Smirnov and Jo{\"e}l Karel and Thomas Suter and {de Boer}, {Rudolf A.} and Dirk Block and Vinzent Rolny and Christian Zaugg and Pfisterer, {Matthias E.} and Ralf Peeters and {Brunner-La Rocca}, Hanspeter",
year = "2018",
month = "6",
doi = "10.1007/s13167-018-0137-7",
language = "English",
volume = "9",
pages = "161--173",
journal = "The EPMA Journal",
issn = "1878-5077",
publisher = "Springer",
number = "2",

}

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, Hanspeter.

In: The EPMA Journal, Vol. 9, No. 2, 06.2018, p. 161-173.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Novel concept to guide systolic heart failure medication by repeated biomarker testing—results from TIME-CHF in context of predictive, preventive, and personalized medicine

AU - Davarzani, Nasser

AU - Sanders-van Wijk, Sandra

AU - Maeder, Micha T.

AU - Rickenbacher, Peter

AU - Smirnov, Evgueni

AU - Karel, Joël

AU - Suter, Thomas

AU - de Boer, Rudolf A.

AU - Block, Dirk

AU - Rolny, Vinzent

AU - Zaugg, Christian

AU - Pfisterer, Matthias E.

AU - Peeters, Ralf

AU - Brunner-La Rocca, Hanspeter

PY - 2018/6

Y1 - 2018/6

N2 - 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 = 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, beta-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). beta-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.

AB - 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 = 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, beta-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). beta-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.

KW - Heart failure

KW - Biomarker

KW - Heart failure medication

KW - Predictive preventive personalized medicine

KW - Generalized estimating equations

KW - LONGITUDINAL DATA-ANALYSIS

KW - BLOOD UREA NITROGEN

KW - NATRIURETIC PEPTIDE

KW - ESTIMATING EQUATIONS

KW - TYROSINE KINASE-1

KW - DISEASE SEVERITY

KW - ELDERLY-PATIENTS

KW - THERAPY

KW - MORTALITY

KW - MANAGEMENT

U2 - 10.1007/s13167-018-0137-7

DO - 10.1007/s13167-018-0137-7

M3 - Article

VL - 9

SP - 161

EP - 173

JO - The EPMA Journal

JF - The EPMA Journal

SN - 1878-5077

IS - 2

ER -