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 pre-determined 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.
| Original language | English |
|---|---|
| Pages (from-to) | 1767-1777 |
| Number of pages | 11 |
| Journal | European Journal of Heart Failure |
| Volume | 24 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Oct 2022 |
| Externally published | Yes |
Bibliographical note
Funding Information:The UMCG, which employs Dr. de Boer, has received research grants and/or fees from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals Gmbh, Ionis Pharmaceuticals, Inc., Novo Nordisk, and Roche (outside the submitted work). R.A.d.B. received speaker fees from Abbott, AstraZeneca, Bayer, Novartis, and Roche (outside the submitted work). J.N. reports personal fees from AstraZeneca, Novartis, Boehringer Ingelheim, Eli Lilly, Rovi, Novo Nordisk, and Vifor Pharma (outside the submitted work). All other authors have nothing to disclose. Pardeep Jhund, my employer, the University of Glasgow, has been remunerated for my time working on clinical trials and associated work by AstraZeneca, Novartis, Bayer AG and NovoNordisk, research funding from AstraZeneca, Boehringer Ingelheim, Analog Devices Inc, Speakers and advisory board fees from AstraZeneca, Novartis, Alkem Metabolics, ProAdWise Communications, Sun Pharmaceuticals. Faiez Zannad, consulting and Trial oversight committees fees from Amgen, Applied Therapeutics, AstraZeneca, Bayer, BMS, Boehringer, Cardior, Cellprothera, Cereno Scientific, CEVA, CVRx, G3Pharmaceutical, Merck, Novartis, NovoNordisk, Servier, Vifor‐Fresenius. Founder of CardioRenal, CVCT, Eshmoun. Christian Mueller has received research support from the Swiss National Science Foundation, the Swiss Heart Foundation, the KTI, the University Hospital Basel, the University of Basel; Abbott, Beckman Coulter, Brahms, Idorsia, Novartis, Ortho Diagnostics, Quidel, Roche, Siemens, Singulex, Sphingotec outside the submitted work, as well as speaker honoraria/consulting honoraria from Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, BMS, Novartis, Osler, Roche, SpinChip, and Sanofi, all paid to the institution. Javed Butler reports consultant Abbott, Adrenomed, Amgen, Applied Therapeutics, Array, AstraZeneca, Bayer, Boehringer Ingelheim, CVRx, G3 Pharma, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Relypsa, Sequana Medical, and Vifor Pharma. James L Januzzi is a Trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals; a Director at Jana Care; has received grant support from Abbott, Applied Therapeutics, HeartFlow, Innolife, and Roche Diagnostics; has received consulting income from Abbott, Beckman, Bristol Myers, Boehringer‐Ingelheim, Janssen, Novartis, Pfizer, Merck, Roche Diagnostics and Siemens; and participates in clinical endpoint committees/data safety monitoring boards for Abbott, AbbVie, CVRx, Intercept, and Takeda. John R. Teerlink has received 3ive Labs, Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol‐Myers Squibb, Cytokinetics, Medtronic, Merck, Novartis, Verily, ViCardia, Windtree Therapeutics and Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol‐Myers Squibb, Cardurion, Cytokinetics, EBR Systems, Medtronic, Novartis, ViCardia, Windtree Therapeutics. Dr. Anker declares grants and personal fees from Vifor and Abbott Vascular, and personal fees for consultancies, trial committee work and/or lectures from Actimed, Astra Zeneca, Amgen, Bayer, Boehringer Ingelheim, Bioventrix, Brahms, Cardiac Dimensions, Cardior, Cordio, CVRx, Edwards, Farraday, Impulse Dynamics, Janssen, Novartis, Occlutech, Pfizer, Respicardia, Servier, and V‐Wave. Dr. Anker also declares that he is named co‐inventor of two patent applications regarding MR‐proANP (DE 102007010834 & DE 102007022367), but he does not benefit personally from the related issued patents. Andrew Coats declares having received honoraria and/or lecture fees from: Astra Zeneca, Bayer, Boehringer Ingelheim, Edwards, Menarini, Novartis, Servier, Vifor, Abbott, Actimed, Arena, Cardiac Dimensions, Corvia, CVRx, Enopace, ESN Cleer, Faraday, Impulse Dynamics, Respicardia, Viatris. Petar Seferovic, Honorarium for lecture: Servier, Astra Zeneca, Menarini Consultancy agreement and honorarium for lecture: Boehringer Ingelheim, Novartis and Roche diagnostic. Dr. Metra received the following personal fees of minimal amounts since January 2021: from Actelion, Amgen, Livanova, and Vifor pharma as member of Executive or Data Monitoring Committees of sponsored clinical trials; from Astra‐Zeneca, Bayer, Boheringer Ingelhelm, Edwards Lifesciences, Novartis for participation to advisory boards and/or speeches at sponsored meetings. J. Lupon reports a relationship with Critical Diagnostics. Gerasimos Filipattos reports being Committee member of Medtronic, Vifor, Amgen, serrvier, Novartis; DSMB for Bayer and Boehringer Ingelheim; payment for lecture for Bayer, Boehringer Ingelheim. Antoni Bayes‐Genis reports personal fees and/ or board meeting participation for Abbott, AstraZeneca, Boehringer Ingelheim, Novartis, Roche Diagnostics, Vifor Pharma. Conflict of interest: Consulting Fees from Contracted Research from
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