1. Prognostic Impact of Repeated NT-proBNP Measurements in Patients With Heart Failure With Reduced Ejection Fraction.
- Author
-
Fuery MA, Leifer ES, Samsky MD, Sen S, O'Connor CM, Fiuzat M, Ezekowitz J, Piña I, Whellan D, Mark D, Felker GM, Desai NR, Januzzi JL, and Ahmad T
- Subjects
- Humans, Prognosis, Stroke Volume, Natriuretic Peptide, Brain therapeutic use, Peptide Fragments, Biomarkers, Chronic Disease, Heart Failure therapy
- Abstract
Background: Although clinical studies have demonstrated the association between a single N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurement and clinical outcomes in chronic heart failure, the biomarker is frequently measured serially in clinical practice., Objectives: The aim of this study was to determine the added prognostic value of repeated NT-proBNP measurements compared with single measurements alone for chronic heart failure patients., Methods: In the GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) study, 894 study participants with chronic heart failure with reduced ejection fraction were enrolled at 45 outpatient sites in the United States and Canada. Repeated NT-proBNP levels were measured over a 2-year study period. Associations between repeated NT-proBNP measurements and trial endpoints were assessed using a joint longitudinal and survival model., Results: After adjustment for baseline covariates, each doubling of the baseline NT-proBNP level was associated with a HR of 1.17 (95% CI: 1.08-1.28; P = 0.0003) for the primary trial endpoint of cardiovascular death or heart failure hospitalization. Serial measurements increased the adjusted HR for the primary trial endpoint to 1.66 (95% CI: 1.50-1.84; P < 0.0001), and a similar increased risk was observed across secondary trial endpoints. In joint modeling, an increase in NT-proBNP occurred weeks before the onset of adjudicated events., Conclusions: Repeated NT-proBNP measurements are a strong predictor of outcomes in heart failure with reduced ejection fraction with an increase in concentration occurring well before event onset. These results may support routine NT-proBNP monitoring to assist in clinical decision making. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure [GUIDE-IT]; NCT01685840)., Competing Interests: Funding Support and Author Disclosures The GUIDE-IT trial was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Additional substudies were supported by Roche Diagnostics. The sponsors had no role in the design and conduct of the present study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Dr O’Connor has received grant or research support from Merck; and has received consulting fees from Merck, Bayer, and Abiomed. Dr Fiuzat has received grant support from the National Institutes of Health and Roche Diagnostics. Dr Ezekowitz has received research grant support and consulting fees from Bayer, Merck, Servier, Amgen, Sanofi, Novartis, Cytokinetics, American Regent, Otsuka, and Applied Therapeutics. Dr Piña has participated on Advisory Boards for Vifor and AstraZeneca; and is a Steering Committee member for Novartis. Dr Whellan has received grants from National Heart, Lung, and Blood Institute, Merck, Amgen, Cytokinetcis, and Norvo Nordisk; has acted as a consultant to Cytokinetics and Novo Nordisk; and has served on Clinical Endpoint Committees/Data and Safety Monitoring Boards for CVRx and National Institutes of Health. Dr Mark reports grant support to institution from HeartFlow and Merck. Dr Felker has received research grants from National Heart, Lung, and Blood Institute, American Heart Association, Amgen, Bayer, BMS, Merck, Cytokinetics, and CSL-Behring; has acted as a consultant to Novartis, Amgen, BMS, Cytokinetics, Innolife, Medtronic, Cardionomic, Boehringer-Ingelheim, American Regent, Abbott, AstraZeneca, Regeneron, Reprieve, Myovant, Sequana, Windtree Therapuetics, Rocket Pharma, and Whiteswell; and has served on Clinical Endpoint Committees/Data and Safety Monitoring Boards for Amgen, Merck, Medtronic, EBR Systems, V-Wave, and LivaNova. Dr Desai works under contract with the Centers for Medicare and Medicaid Services to develop and maintain performance measures used for public reporting and pay for performance programs; and reports research grants and consulting for Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cytokinetics, Novartis, SCPharmaceuticals, and Vifor. Dr Januzzi is a Trustee of the American College of Cardiology and a Director at Jana Care and Imbria; has received grant support from Abbott, Applied Therapeutics, HeartFlow Inc, Innolife, and Roche Diagnostics, has received consulting income from Abbott, AstraZeneca, Beckman-Coulter, Boehringer-Ingelheim, Janssen, Novartis, Merck, Quidel, Roche Diagnostics, and Siemens; and participates in Clinical Endpoint Committees/Data and Safety Monitoring boards for Abbott, AbbVie, Bayer, CVRx, Pfizer, and Takeda. Dr Ahmad has received consulting fees from Sanofi, Amgen, and Cytokinetics; and has received research funding from Boehringer Ingelheim, AstraZeneca, Cytokinetics, and Relypsa. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF