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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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
Issue number2
Publication statusPublished - Jun 2018


  • Heart failure
  • Biomarker
  • Heart failure medication
  • Predictive preventive personalized medicine
  • Generalized estimating equations


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