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 N 1Department of Data Science and Knowledge Engineering, Maastricht University, St. Servaasklooster 39, P.O. Box 616, 6200 MD Maastricht, the Netherlands.
- Sanders-van Wijk S 2Department of Cardiology, Maastricht University Medical Center, Maastricht, the Netherlands.
- Maeder MT 4Department of Cardiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
- Rickenbacher P Division of Cardiology, University Hospital Bruderholz, Bruderholz, Switzerland.
- Smirnov E 1Department of Data Science and Knowledge Engineering, Maastricht University, St. Servaasklooster 39, P.O. Box 616, 6200 MD Maastricht, the Netherlands.
- Karel J 1Department of Data Science and Knowledge Engineering, Maastricht University, St. Servaasklooster 39, P.O. Box 616, 6200 MD Maastricht, the Netherlands.
- Suter T 6Department of Cardiology, University Hospital Berne, Berne, Switzerland.
- de Boer RA 7Department of Cardiology, University Medical Center Groningen, Groningen, the Netherlands.
- Block D 8Roche Diagnostics GmbH, Penzberg, Germany.
- Rolny V 8Roche Diagnostics GmbH, Penzberg, Germany.
- Zaugg C Roche Diagnostics International, Rotkreuz, Switzerland.
- Pfisterer ME 10Department of Cardiology, University Hospital Basel, Basel, Switzerland.
- Peeters R 1Department of Data Science and Knowledge Engineering, Maastricht University, St. Servaasklooster 39, P.O. Box 616, 6200 MD Maastricht, the Netherlands.
- Brunner-La Rocca HP 2Department of Cardiology, Maastricht University Medical Center, Maastricht, the Netherlands.
- 2018-06-14
Published in:
- The EPMA journal. - 2018
Biomarker
Generalized estimating equations
Heart failure
Heart failure medication
Predictive preventive personalized medicine
English
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.
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.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1007/s13167-018-0137-7
- PMID 29896315
- Persistent URL
- https://sonar.ch/global/documents/145114
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