Natriuretic Peptide Response and Outcomes in Chronic Heart Failure With Reduced Ejection Fraction

Abstract

Background: The GUIDE-IT (GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) trial demonstrated that a strategy to "guide" application of guideline-directed medical therapy (GDMT) by reducing amino-terminal pro-B-type natriuretic peptide (NT-proBNP) was not superior to GDMT alone.

Objectives: The purpose of this study was to examine the prognostic meaning of NT-proBNP changes following heart failure (HF) therapy intensification relative to the goal NT-proBNP value of 1,000 pg/ml explored in the GUIDE-IT trial.

Methods: A total of 638 study participants were included who were alive and had available NT-proBNP results 90 days after randomization. Rates of subsequent cardiovascular (CV) death/HF hospitalization or all-cause mortality during follow-up and Kansas City Cardiomyopathy Questionnaire (KCCQ) overall scores were analyzed.

Results: A total of 198 (31.0%) subjects had an NT-proBNP ≤1,000 pg/ml at 90 days with no difference in achievement of NT-proBNP goal between the biomarker-guided and usual care arms. NT-proBNP ≤1,000 pg/ml by 90 days was associated with longer freedom from CV/HF hospitalization or all-cause mortality (p < 0.001 for both) and lower adjusted hazard of subsequent HF hospitalization/CV death (hazard ratio: 0.26; 95% confidence interval: 0.15 to 0.46; p < 0.001) and all-cause mortality (hazard ratio: 0.34; 95% confidence interval: 0.15 to 0.77; p = 0.009). Regardless of elevated baseline concentration, an NT-proBNP ≤1,000 pg/ml at 90 days was associated with better outcomes and significantly better KCCQ overall scores (p = 0.02).

Conclusions: Patients with heart failure with reduced ejection fraction whose NT-proBNP levels decreased to ≤1,000 pg/ml during GDMT had better outcomes. These findings may help to understand the results of the GUIDE-IT trial. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment [GUIDE-IT]; NCT01685840).

Keywords: heart failure; natriuretic peptides; outcomes.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

Central Illustration:. Natriuretic Peptide Response in Heart Failure Treatment.

Cumulative event curves showing the probability of experiencing the outcomes by time in subjects with NT-proBNP ≤1000 pg/mL and those with NT-proBNP >1000 pg/mL at 90 days. A) CV death or HF hospitalization and B) all-cause mortality as a function of NT-proBNP concentrations. Those with concentrations of NT-proBNP ≤1000 pg/mL at 90 days had lower rates of subsequent events.

Central Illustration:. Natriuretic Peptide Response in Heart Failure Treatment.

Cumulative event curves showing the probability of experiencing the outcomes by time in subjects with NT-proBNP ≤1000 pg/mL and those with NT-proBNP >1000 pg/mL at 90 days. A) CV death or HF hospitalization and B) all-cause mortality as a function of NT-proBNP concentrations. Those with concentrations of NT-proBNP ≤1000 pg/mL at 90 days had lower rates of subsequent events.

Figure 1:. Study flow diagram.

Patients free of clinical events prior to 90 days following randomization were included.

Figure 2:. Rates of CV death or HF hospitalization and all-cause mortality as a function of NT-proBNP categories at 90 days.

Higher concentrations of NT-proBNP by 90 days after randomization were associated with worse outcomes.

Figure 3:. Outcomes in GUIDE-IT as a function of change in NT-proBNP response categories from baseline to 90 days.

Patients were considered as “low-low” if ≤1000 pg/mL at both time points, “low-high” if ≤1000 pg/mL at baseline/>1000 pg/mL at 90 days, “high-low” if >1000 pg/mL at baseline/≤1000 pg/mL at 90 days, and “high-high” if >1000 pg/mL at both time points. A) Cox proportional hazards analyses and cumulative event curves for B) HF hospitalization/CV death or C) all-cause mortality show superior subsequent outcomes among those with NT-proBNP ≤1000 pg/mL at baseline and/or 90 days. The hazard ratio is adjusted for baseline NT-proBNP.

Figure 3:. Outcomes in GUIDE-IT as a function of change in NT-proBNP response categories from baseline to 90 days.

Patients were considered as “low-low” if ≤1000 pg/mL at both time points, “low-high” if ≤1000 pg/mL at baseline/>1000 pg/mL at 90 days, “high-low” if >1000 pg/mL at baseline/≤1000 pg/mL at 90 days, and “high-high” if >1000 pg/mL at both time points. A) Cox proportional hazards analyses and cumulative event curves for B) HF hospitalization/CV death or C) all-cause mortality show superior subsequent outcomes among those with NT-proBNP ≤1000 pg/mL at baseline and/or 90 days. The hazard ratio is adjusted for baseline NT-proBNP.

Figure 3:. Outcomes in GUIDE-IT as a function of change in NT-proBNP response categories from baseline to 90 days.

Patients were considered as “low-low” if ≤1000 pg/mL at both time points, “low-high” if ≤1000 pg/mL at baseline/>1000 pg/mL at 90 days, “high-low” if >1000 pg/mL at baseline/≤1000 pg/mL at 90 days, and “high-high” if >1000 pg/mL at both time points. A) Cox proportional hazards analyses and cumulative event curves for B) HF hospitalization/CV death or C) all-cause mortality show superior subsequent outcomes among those with NT-proBNP ≤1000 pg/mL at baseline and/or 90 days. The hazard ratio is adjusted for baseline NT-proBNP.

Figure 4:. Box-and-whisker plot of the Kansas City Cardiomyopathy Questionnaire (KCCQ) at 90 days as a function of NT-proBNP at this same time point.

Lower NT-proBNP was associated with higher KCCQ scores, consistent with superior quality of life. Median values are the black line, boxes represent the 25th and 75th percentiles, and whiskers detail the 5th and 95th percentiles.

Figure 5:

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