Never has a biomarker with so much evidence demonstrating its disutility, enjoyed such a long reign of prosperity as BNP and its natriuretic analogs. And while evidence discrediting BNP’s use for the diagnosis and inpatient management of acute exacerbations of heart failure (HF) is well documented, its utility to guide outpatient therapy in patients with HF has not yet been invalidated. Although I have discussed the issues with the use of these assays in the Emergency Department in previous posts, I never shy away from a good natriuretic bashing session.
A recent article published in JAMA by Felker et al examined the therapeutic benefits of an outpatient natriuretic peptide guided strategy for patients with CHF with reduced ejection fraction (HFrEF) (1). The authors enrolled patients with chronic HFrEF (ejection fraction < 40%), a history of a prior HF event (hospitalization for HF, emergency department visit for HF, or outpatient treatment with intravenous diuretics for HF) within the prior 12 months, and an NT-proBNP level of more than 2000 pg/mL or BNP of more than 400 pg/mL, within 30 days prior. Patients were randomized to either a natriuretic peptide guided strategy, in which clinicians were instructed to titrate HF therapy to target an NT-proBNP level of less than 1000 pg/mL, or standard care. Titration of specific medications was left to the discretion of the treating clinician. All patients had blinded NT-proBNP concentrations, drawn at each study visit (2 and 6 weeks, and every 3 months following).
Over a two and a half year period the authors enrolled 894 patients, stopping short of their intended enrollment goal of 1100 due to futility. Despite patients randomized to the natriuretic guided strategy demonstrating a greater number of clinic visits and more aggressive titration of HF medication, the authors found no difference in their primary outcome, the composite of time-to-first HF hospitalization or death from cardiovascular causes. Nor did they observe a difference in any of their prespecified secondary endpoints, all-cause mortality, total HF related hospitalizations, health-related quality of life, resource utilization, or safety.
This is as negative a trial as one could imagine. Given natriuretic peptides’ abysmal track record, these results are not surprising. What this study does provide is clear evidence that the statement often uttered by natriuretic peptide apologists, ‘while BNP, when examined in singularity is not helpful, over time the temporal trends can provide guidance’ is factually incorrect.
It is doubtful these results will change practice. The natriuretic peptides have suffered seemingly lethal injuries and emerged unscathed. They appear all but resistant to scientific inquiry. The Felker et al manuscript provides additional evidence against the utility of ordering these assays in the Emergency Department on the chance they will benefit downstream providers’ care. The use of natriuretic peptides has been disproven as a diagnostic tool in the Emergency Department. They have time and time again proven themselves unhelpful in the inpatient setting. And now even their use to guide outpatient therapy has been discredited.
- Felker GM, Anstrom KJ, Adams KF, Ezekowitz JA, Fiuzat M, Houston-Miller N, Januzzi JL, Mark DB, Piña IL, Passmore G, Whellan DJ, Yang H, Cooper LS, Leifer ES, Desvigne-Nickens P, O’Connor CM. 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(8):713–720.