Use of Amino-Terminal Pro–B-Type Natriuretic Peptide to Guide Outpatient Therapy of Patients With Chronic Left Ventricular Systolic Dysfunction

Study Questions:

Does targeting N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels to <1000 pg/ml improve outcomes compared with standard optimal care (SOC) in adults with systolic heart failure (HF)?


This was a single-center, nonblinded, randomized trial. Patients with systolic HF (ejection fraction ≤40%) were block randomized by New York Heart Association (NYHA) class to assessment of serum NT-proBNP levels versus SOC without NT-proBNP assessment. In the NT-proBNP arm, the aim was to titrate HF therapy per clinician discretion to achieve an NT-proBNP level <1000 pg/ml. The primary outcome of interest was the composite of worsening HF, hospitalization for HF, clinically significant ventricular arrhythmia, ischemic stroke, acute coronary syndrome, or sudden cardiac death. General estimating equations were used for analysis, and adjusted logistic odds ratios are provided for the primary endpoint below.


The mean ± standard deviation patient age was 63 ± 14 years and 86% were NYHA class II or III. There were a median of five clinic visits over 10 ± 3 months of follow-up. NT-proBNP levels were comparable at baseline between the intervention (2344 pg/ml) and SOC (1946 pg/ml) groups, but only the intervention group had a significant reduction in NT-proBNP levels at the study’s end (to 1125 pg/ml, p = 0.01 vs. baseline). The <1000 pg/ml NT-proBNP goal was reached in 44% and 36% of intervention and SOC patients, respectively. Patients in the NT-proBNP arm had a log odds 0.44 (95% confidence interval, 0.22-0.84) fewer events (n = 58) than those receiving SOC (n = 100, p = 0.009). This event reduction was mainly driven by a reduction in worsening HF and HF admissions. Compared with SOC, patients in the NT-proBNP arm had better quality-of-life measures and achieved an 8% increase in left ventricular ejection fraction without an increased incidence of adverse events.


The authors concluded that in patients with systolic HF, NT-proBNP guided care improves outcomes and leads to significant improvements in left ventricular remodeling.


The use of natriuretic peptides to guide HF management has been met with mixed results in clinical trials. In this single-center study, targeting NT-proBNP to values <1000 pg/ml appeared to have an impact on cardiovascular outcomes, especially HF exacerbations. Like other studies, more patients in the NT-proBNP monitoring arm were on aldosterone antagonists at the study’s end, and trends suggested improved dosing of beta-blockers and angiotensin-converting enzyme inhibitors with peptide monitoring. What is different in this analysis from many others is that patients in the NT-proBNP arm were actually less likely to be taking diuretics at the study’s end. This is the appropriate clinical response to natriuretic peptide elevation since diuretics do not improve the underlying neurohormonal dysregulation. Natriuretic-guided therapy studies are all limited by lack of blinding. An ejection fraction increase of 8% over 10 months is impressive for any HF trial, but needs to be interpreted with some skepticism. It would be interesting to note if there was a correlation between NT-proBNP level and clinic visit frequency or medication titration. It would also be interesting to know why physicians in the SOC arm did not choose to titrate evidence-based medications at follow-up. The question remains if NT-proBNP monitoring alone serves as a reminder ‘trigger’ for physicians to titrate medications or if the elevation in levels provokes clinical intervention.

Clinical Topics: Acute Coronary Syndromes, Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, ACS and Cardiac Biomarkers, SCD/Ventricular Arrhythmias, Acute Heart Failure, Chronic Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Stroke, Acute Coronary Syndrome, Ventricular Function, Left, Mineralocorticoid Receptor Antagonists, Diuretics, Heart Failure, Systolic, Heart Diseases, Ventricular Remodeling, Stroke Volume, Atrial Natriuretic Factor, Hospitalization, Death, Sudden, Cardiac, Natriuretic Peptide, Brain

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