Biomarkers in heart failure clinical trials. A review from the Biomarkers Working Group of the Heart Failure Association of the European Society of Cardiology.
-Omics
Biomarkers
Clinical trials
Criteria
Inclusion
Natriuretic peptides
Risk prediction
Journal
European journal of heart failure
ISSN: 1879-0844
Titre abrégé: Eur J Heart Fail
Pays: England
ID NLM: 100887595
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
revised:
29
08
2022
received:
06
06
2022
accepted:
31
08
2022
pubmed:
9
9
2022
medline:
29
11
2022
entrez:
8
9
2022
Statut:
ppublish
Résumé
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.
Substances chimiques
sacubitril
17ERJ0MKGI
Angiotensin Receptor Antagonists
0
Tetrazoles
0
Aminobutyrates
0
Valsartan
80M03YXJ7I
Biphenyl Compounds
0
Biomarkers
0
Drug Combinations
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1767-1777Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2022 European Society of Cardiology.
Références
Januzzi JL Jr, Canty JM, Das S, DeFilippi CR, Gintant GA, Gutstein DE, et al. Gaining efficiency in clinical trials with cardiac biomarkers: JACC review topic of the week. J Am Coll Cardiol. 2021;77:1922-33.
Statista. Success rate of novel cardiovascular disease drugs by development phase in the United States in 2008-2019. https://www.statista.com/statistics/1186648/us-clinical-development-success-rate-novel-cardiovascular-drugs (accessed 13 September 2022).
Biotechnology Innovation Organization. Clinical Development Success Rates 2006-2015. June 2016. https://www.bio.org/sites/default/files/legacy/bioorg/docs/Clinical%20Development%20Success%20Rates%202006-2015%20-%20BIO,%20Biomedtracker,%20Amplion%202016.pdf (accessed 13 September 2022).
Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Therapeut. 2001;69:89-95.
Castiglione V, Aimo A, Vergaro G, Saccaro L, Passino C, Emdin M. Biomarkers for the diagnosis and management of heart failure. Heart Fail Rev. 2022;27:625-43.
Ibrahim NE, Burnett JC Jr, Butler J, Camacho A, Felker GM, Fiuzat M, et al. Natriuretic peptides as inclusion criteria in clinical trials: a JACC: Heart Failure position paper. JACC Heart Fail. 2020;8:347-58.
U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER). FDA Draft Guidance: Treatment for Heart Failure: Endpoints for Drug Development Guidance for Industry. Silver Spring, MD: Food and Drug Administration; 2019.
Ahmad T, Fiuzat M, Pencina MJ, Geller NL, Zannad F, Cleland JG, et al. Charting a roadmap for heart failure biomarker studies. JACC Heart Fail. 2014;2:477-88.
van Kimmenade RR, Januzzi JL Jr. Emerging biomarkers in heart failure. Clin Chem. 2012;58:127-38.
Braunwald E. The war against heart failure: the Lancet lecture. Lancet. 2015;385:812-24.
González A, Richards AM, de Boer RA, Thum T, Arfsten H, Hülsmann M, et al. Cardiac remodelling - part 1: from cells and tissues to circulating biomarkers. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2022;24:927-43.
Ibrahim NE, Gaggin HK, Konstam MA, Januzzi JL Jr. Established and emerging roles of biomarkers in heart failure clinical trials. Circ Heart Fail. 2016;9.
Mueller C, McDonald K, de Boer RA, Maisel A, Cleland JGF, Kozhuharov N, et al.; Heart Failure Association of the European Society of Cardiology. Heart Failure Association of the European Society of Cardiology practical guidance on the use of natriuretic peptide concentrations. Eur J Heart Fail. 2019;21:715-31.
Braunwald E. Biomarkers in heart failure. N Engl J Med. 2008;358:2148-59.
Ibrahim NE, Januzzi JL Jr. Beyond natriuretic peptides for diagnosis and management of heart failure. Clin Chem. 2017;63:211-22.
Vasan RS. Biomarkers of cardiovascular disease: molecular basis and practical considerations. Circulation. 2006;113:2335-62.
Emdin M, Vittorini S, Passino C, Clerico A. Old and new biomarkers of heart failure. Eur J Heart Fail. 2009;11:331-5.
Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Omland T, et al. Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N Engl J Med. 2004;350:655-63.
Ledwidge M, Gallagher J, Conlon C, Tallon E, O'Connell E, Dawkins I, et al. Natriuretic peptide-based screening and collaborative care for heart failure: the STOP-HF randomized trial. JAMA. 2013;310:66-74.
Huelsmann M, Neuhold S, Resl M, Strunk G, Brath H, Francesconi C, et al. PONTIAC (NT-proBNP selected prevention of cardiac events in a population of diabetic patients without a history of cardiac disease): a prospective randomized controlled trial. J Am Coll Cardiol. 2013;62:1365-72.
Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association joint committee on clinical practice guidelines. Circulation. 2022;145:e895-e1032.
McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al.; ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2022;24:4-131.
Bozkurt B, Coats AJ, Tsutsui H, Abdelhamid M, Adamopoulos S, Albert N, et al. Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure. Eur J Heart Fail. 2021;23:352-80.
Lau ES, Binek A, Parker SJ, Shah SH, Zanni MV, Van Eyk JE, et al. Sexual dimorphism in cardiovascular biomarkers: clinical and research implications. Circ Res. 2022;130:578-92.
Moura B, Aimo A, Al-Mohammad A, Flammer A, Barberis V, Bayes-Genis A, et al. Integration of imaging and circulating biomarkers in heart failure: a consensus document by the Biomarkers and Imaging Study Groups of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2021;23:1577-96.
Felker GM, Anstrom KJ, Adams KF, Ezekowitz JA, Fiuzat M, Houston-Miller N, et al. Effect of natriuretic peptide-guided therapy on hospitalization or cardiovascular mortality in high-risk patients with heart failure and reduced ejection fraction: a randomized clinical trial. JAMA. 2017;318:713-20.
Zile MR, Claggett BL, Prescott MF, McMurray JJ, Packer M, Rouleau JL, et al. Prognostic implications of changes in N-terminal pro-B-type natriuretic peptide in patients with heart failure. J Am Coll Cardiol. 2016;68:2425-36.
Medscape. FDA Clears Sacubitril/Valsartan for Children With Heart Failure. October 3, 2019. https://www.medscape.com/viewarticle/919362 (accessed 13 September 2022).
Januzzi JL Jr, Rehman S, Mueller T, van Kimmenade RR, Lloyd-Jones DM. Importance of biomarkers for long-term mortality prediction in acutely dyspneic patients. Clin Chem. 2010;56:1814-21.
Daubert MA, Adams K, Yow E, Barnhart HX, Douglas PS, Rimmer S, et al. NT-proBNP goal achievement is associated with significant reverse remodeling and improved clinical outcomes in HFrEF. JACC Heart Fail. 2019;7:158-68.
Solomon SD, McMurray JJV, Anand IS, Ge J, Lam CSP, Maggioni AP, et al.; PARAGON-HF Investigators and Committees. Angiotensin-neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med. 2019;381:1609-20.
Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M, et al.; EMPEROR-Preserved Trial Investigators. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385:1451-61.
Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, et al.; TOPCAT Investigators. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014;370:1383-92.
Solomon SD, de Boer RA, DeMets D, Hernandez AF, Inzucchi SE, Kosiborod MN, et al. Dapagliflozin in heart failure with preserved and mildly reduced ejection fraction: rationale and design of the DELIVER trial. Eur J Heart Fail. 2021;23:1217-25.
Myhre PL, Vaduganathan M, Claggett BL, Anand IS, Sweitzer NK, Fang JC, et al. Association of natriuretic peptides with cardiovascular prognosis in heart failure with preserved ejection fraction: secondary analysis of the TOPCAT randomized clinical trial. JAMA Cardiol. 2018;3:1000-5.
Pabón MA, Cunningham JW, Claggett BL, Packer M, Zile M, Pfeffer MA, et al. Natriuretic peptide-based inclusion criteria in heart failure with preserved ejection fraction clinical trials: insights from PARAGON-HF. Eur J Heart Fail. 2022;24:672-7.
Januzzi JL, van Kimmenade R, Lainchbury J, Bayes-Genis A, Ordonez-Llanos J, Santalo-Bel M, et al. NT-proBNP testing for diagnosis and short-term prognosis in acute destabilized heart failure: an international pooled analysis of 1256 patients: the International Collaborative of NT-proBNP Study. Eur Heart J. 2006;27:330-7.
Rehman SU, Martinez-Rumayor A, Mueller T, Januzzi JL Jr. Independent and incremental prognostic value of multimarker testing in acute dyspnea: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study. Clin Chim Acta. 2008;392:41-5.
van Veldhuisen DJ, Linssen GC, Jaarsma T, van Gilst WH, Hoes AW, Tijssen JG, et al. B-type natriuretic peptide and prognosis in heart failure patients with preserved and reduced ejection fraction. J Am Coll Cardiol. 2013;61:1498-506.
McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al.; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993-1004.
Packer M, Fowler MB, Roecker EB, Coats AJ, Katus HA, Krum H, et al.; Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) Study Group. Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) study. Circulation. 2002;106:2194-9.
Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999;353:2001-7.
Motiwala SR, Szymonifka J, Belcher A, Weiner RB, Baggish AL, Sluss P, et al. Serial measurement of galectin-3 in patients with chronic heart failure: results from the ProBNP Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) study. Eur J Heart Fail. 2013;15:1157-63.
Ezekowitz JA, O'Connor CM, Troughton RW, Alemayehu WG, Westerhout CM, Voors AA, et al. N-terminal pro-B-type natriuretic peptide and clinical outcomes: Vericiguat Heart Failure With Reduced Ejection Fraction study. JACC Heart Fail. 2020;8:931-9.
Januzzi JL Jr, Prescott MF, Butler J, Felker GM, Maisel AS, McCague K, et al.; PROVE-HF Investigators. Association of change in N-terminal pro-B-type natriuretic peptide following initiation of sacubitril-valsartan treatment with cardiac structure and function in patients with heart failure with reduced ejection fraction. JAMA. 2019;322:1085-95.
Murphy SP, Prescott MF, Maisel AS, Butler J, Piña IL, Felker GM, et al. Association between angiotensin receptor-neprilysin inhibition, cardiovascular biomarkers, and cardiac remodeling in heart failure with reduced ejection fraction. Circ Heart Fail. 2021;14:e008410.
Ozkara A, Turgut F, Selcoki Y, Karanfil A, Metin MR, Kanbay M, et al. Probrain natriuretic peptide for assessment of efficacy in heart failure treatment. Adv Ther. 2007;24:1233-9.
Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, et al.; EMPEROR-Reduced Trial Investigators. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383:1413-24.
Vallon V, Verma S. Effects of SGLT2 inhibitors on kidney and cardiovascular function. Annu Rev Physiol. 2021;83:503-28.
Pocock SJ, Ferreira JP, Gregson J, Anker SD, Butler J, Filippatos G, et al. Novel biomarker-driven prognostic models to predict morbidity and mortality in chronic heart failure: the EMPEROR-Reduced trial. Eur Heart J. 2021;42:4455-64.
Brown PM, Ezekowitz JA. Composite end points in clinical trials of heart failure therapy: how do we measure the effect size? Circ Heart Fail. 2017;10:e003222.
Packer M. Development and evolution of a hierarchical clinical composite end point for the evaluation of drugs and devices for acute and chronic heart failure: a 20-year perspective. Circulation. 2016;134:1664-78.
Felker GM, Maisel AS. A global rank end point for clinical trials in acute heart failure. Circ Heart Fail. 2010;3:643-6.
Zannad F, Garcia AA, Anker SD, Armstrong PW, Calvo G, Cleland JG, et al. Clinical outcome endpoints in heart failure trials: a European Society of Cardiology Heart Failure Association consensus document. Eur J Heart Fail. 2013;15:1082-94.
Voors AA, Angermann CE, Teerlink JR, Collins SP, Kosiborod M, Biegus J, et al. The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nat Med. 2022;28:568-74.
Ferreira JP, Jhund PS, Duarte K, Claggett BL, Solomon SD, Pocock S, et al. Use of the win ratio in cardiovascular trials. JACC Heart Fail. 2020;8:441-50.
Pocock SJ, Ariti CA, Collier TJ, Wang D. The win ratio: a new approach to the analysis of composite endpoints in clinical trials based on clinical priorities. Eur Heart J. 2012;33:176-82.
Braunwald E. Heart failure. JACC Heart Fail. 2013;1:1-20.
Verbrugge FH, Omote K, Reddy YNV, Sorimachi H, Obokata M, Borlaug BA. Heart failure with preserved ejection fraction in patients with normal natriuretic peptide levels is associated with increased morbidity and mortality. Eur Heart J. 2022;43:1941-51.
Curigliano G, Cardinale D, Suter T, Plataniotis G, de Azambuja E, Sandri MT, et al.; ESMO Guidelines Working Group. Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO clinical practice guidelines. Ann Oncol. 2012;23:vii155-66.
Yeh ET, Tong AT, Lenihan DJ, Yusuf SW, Swafford J, Champion C, et al. Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management. Circulation. 2004;109:3122-31.
Sawaya H, Sebag IA, Plana JC, Januzzi JL, Ky B, Cohen V, et al. Early detection and prediction of cardiotoxicity in chemotherapy-treated patients. Am J Cardiol. 2011;107:1375-80.
Jabbour A, Hayward CS, Keogh AM, Kotlyar E, McCrohon JA, England JF, et al. Parenteral administration of recombinant human neuregulin-1 to patients with stable chronic heart failure produces favourable acute and chronic haemodynamic responses. Eur J Heart Fail. 2011;13:83-92.
Teerlink JR, Diaz R, Felker GM, McMurray JJV, Metra M, Solomon SD, et al.; GALACTIC-HF Investigators. Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure. N Engl J Med. 2021;384:105-16.
Sherwood MW, Kristin NL. High-sensitivity troponin assays: evidence, indications, and reasonable use. J Am Heart Assoc. 2014;3:e000403.
Meijers WC, van der Velde AR, Muller Kobold AC, Dijck-Brouwer J, Wu AH, Jaffe A, et al. Variability of biomarkers in patients with chronic heart failure and healthy controls. Eur J Heart Fail. 2017;19:357-65.
Du W, Piek A, Schouten EM, van de Kolk CWA, Mueller C, Mebazaa A, et al. Plasma levels of heart failure biomarkers are primarily a reflection of extracardiac production. Theranostics. 2018;8:4155-69.
Cohen-Solal A, Logeart D, Huang B, Cai D, Nieminen MS, Mebazaa A. Lowered B-type natriuretic peptide in response to levosimendan or dobutamine treatment is associated with improved survival in patients with severe acutely decompensated heart failure. J Am Coll Cardiol. 2009;53:2343-8.
Packer M, O'Connor C, McMurray JJV, Wittes J, Abraham WT, Anker SD, et al.; TRUE-AHF Investigators. Effect of ularitide on cardiovascular mortality in acute heart failure. N Engl J Med. 2017;376:1956-64.
Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J, et al. 2021 ESC/EACTS guidelines for the management of valvular heart disease. Eur Heart J. 2022;43:561-632.
Gardezi SK, Coffey S, Prendergast BD, Myerson SG. Serum biomarkers in valvular heart disease. Heart. 2018;104:349-58.
Stone GW, Vahanian AS, Adams DH, Abraham WT, Borer JS, Bax JJ, et al.; Mitral Valve Academic Research Consortium (MVARC). Clinical trial design principles and endpoint definitions for transcatheter mitral valve repair and replacement: part 1: clinical trial design principles: a consensus document from the Mitral Valve Academic Research Consortium. J Am Coll Cardiol. 2015;66:278-307.
Aimo A, Vergaro G, González A, Barison A, Lupón J, Delgado V, et al. Cardiac remodelling - part 2: clinical, imaging and laboratory findings. A review from the Biomarkers Working Group of the Heart Failure Association of the ESC. Eur J Heart Fail. 2022;24:944-58.
Michelhaugh SA, Januzzi JL Jr. Finding a needle in a haystack: proteomics in heart failure. JACC Basic Transl Sci. 2020;5:1043-53.
Michelhaugh SA, Camacho A, Ibrahim NE, Gaggin H, D'Alessandro D, Coglianese E, et al. Proteomic signatures during treatment in different stages of heart failure. Circ Heart Fail. 2020;13:e006794.
Bayes-Genis A, Liu PP, Lanfear DE, de Boer RA, González A, Thum T, et al. Omics phenotyping in heart failure: the next frontier. Eur Heart J. 2020;41:3477-84.
Adamo L, Yu J, Rocha-Resende C, Javaheri A, Head RD, Mann DL. Proteomic signatures of heart failure in relation to left ventricular ejection fraction. J Am Coll Cardiol. 2020;76:1982-94.
Meijers WC, Bayes-Genis A, Mebazaa A, Bauersachs J, Cleland JGF, Coats AJS, et al. Circulating heart failure biomarkers beyond natriuretic peptides: review from the Biomarker Study Group of the Heart Failure Association (HFA), European Society of Cardiology (ESC). Eur J Heart Fail. 2021;23:1610-32.