Prognostic Impact of Repeated NT-proBNP Measurements in Patients With Heart Failure With Reduced Ejection Fraction.

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).