Biomarkers in heart failure clinical trials. A review from the Biomarkers Working Group of the Heart Failure Association of the European Society of Cardiology

Bayes‐Genis, A. et al. (2022) Biomarkers in heart failure clinical trials. A review from the Biomarkers Working Group of the Heart Failure Association of the European Society of Cardiology. European Journal of Heart Failure, 24(10), pp. 1767-1777. (doi: 10.1002/ejhf.2675) (PMID:36073112)

Abstract

The approval of new heart failure (HF) therapies has slowed over the past two decades in part due to the high costs of conducting large randomized clinical trials that are needed to adequately power major clinical endpoint studies. Several biomarkers have been identified reflecting different elements of HF pathophysiology, with possible applications in diagnosis, risk stratification, treatment monitoring, and even in the design of clinical trials. Biomarkers could potentially be used to refine study inclusion criteria to enable enrolment of patients who are more likely to respond to a therapeutic intervention, despite being at sufficient risk to meet predetermined study endpoint rates. When there is a close relationship between biomarker levels and clinical endpoints, changes in biomarker levels after a given treatment can act as a surrogate endpoint, potentially reducing the duration and cost of a clinical trial. Natriuretic peptides have been widely used in clinical trials with a variable amount of added value, which such variation being probably due to the absence of a close pathophysiological connection to the study drug. Notable exceptions to this include sacubitril/valsartan and vericiguat. Future studies should seek to adopt unbiased approaches for discovery of true companion diagnostics; with -omics-based tools, biomarkers might be more precisely selected for use in clinical trials to identify responses that closely reflect the biological effects of the drug under investigation. Finally, biomarkers associated with cardiac damage and remodelling, such as cardiac troponin, could be employed as safety endpoints provided that standardization between different assays is achieved.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jhund, Professor Pardeep
• Authors: Bayes‐Genis, A., Aimo, A., Jhund, P., Richards, A. M., de Boer, R. A., Arfsten, H., Fabiani, I., Lupón, J., Anker, S. D., González, A., Castiglione, V., Metra, M., Mueller, C., Núñez, J., Rossignol, P., Barison, A., Butler, J., Teerlink, J., Filippatos, G., Ponikowski, P., Vergaro, G., Zannad, F., Seferovic, P., Rosano, G., Coats, A. J.S., Emdin, M., and Januzzi, J. L.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: European Journal of Heart Failure
• Publisher: Wiley
• ISSN: 1388-9842
• ISSN (Online): 1879-0844
• Published Online: 08 September 2022
• Copyright Holders: Copyright © 2022 European Society of Cardiology
• First Published: First published in European Journal of Heart Failure 24(10): 1767-1777
• Publisher Policy: Reproduced in accordance with the publisher copyright policy