Physicians' Academy for Cardiovascular Education

NT-proBNP levels predict outcomes in HF patients with or without atrial fibrillation

Prognostic Value of N-Terminal Pro-B-Type Natriuretic Peptide Levels in Heart Failure Patients With and Without Atrial Fibrillation

Literature - Kristensen SL, Jhund PS, Mogensen UM, et al. PARADIGM-HF and ATMOSPHERE Committees and Investigators - Circ Heart Fail. 2017 Oct;10(10). doi: 10.1161/CIRCHEARTFAILURE.117.004409


Higher levels of natriuretic peptides (NP) are associated with higher rates of CV death and heart failure (HF) hospitalization, and are influenced by many factors, including age, obesity, renal function, and atrial fibrillation (AF) [1-3]. NP levels peptides are generally higher in patients with AF, and the prognostic significance of a given NT-proBNP concentration in patients with AF, compared with those without AF, is uncertain.

This study compared the relationship between NT-proBNP concentrations and clinical outcomes in patients with and without AF, using data from 2 trials in patients with HFrEF, which had similar enrolment criteria. The main inclusion criteria for PARADIGM-HF and ATMOSPHERE were [4,5]: NYHA functional class II–IV, EF ≤35% and plasma BNP of ≥150 pg/mL or NT-proBNP of ≥600 pg/mL

In both PARADIGM-HF and ATMOSPHERE, patients first received enalapril (5 or) 10 mg BID (single-blind) and then sacubitril/valsartan (single-blind) for an additional 4 to 6 weeks in PARADIGM-HF and aliskiren plus enalapril in ATMOSPHERE. In PARADIGM-HF, patients tolerating both drugs at target doses were randomly assigned to enalapril 10 mg BID or sacubitril/valsartan 200 mg BID, and in ATMOSPHERE, patients who tolerated both drugs were randomized in a 1:1:1 ratio to receive either the combination of 5 or 10 mg enalapril BID and aliskiren 150 mg OD (combination group), or aliskiren 150 mg OD, or enalapril 5 or 10 mg BID.

Based on their NT-proBNP levels at baseline, patients were categorized as follows: NT-proBNP <400 pg/mL, NT-proBNP: 400-999 pg/mL (reference group), NT-proBNP: 1000-1999 pg/mL, NT-proBNP: 2000-2999 pg/mL or NT-proBNP ≥3000 pg/mL. The primary endpoint was the first occurrence of CV death or HF hospitalization. Other endpoints were CV death and HF hospitalization separately, as well as death from any cause.

Main results


In a meta-analysis of the PARADIGM-HF and ATMOSPHERE trials, any given concentration of NT-proBNP above 400 pg/mL, had a similar predictive value for adverse outcomes in HFrEF patients with and without AF. These data suggest that although NT-proBNP levels are, on average, higher in patients with AF, this does not diminish their prognostic significance. Thus, this does not justify the now common policy to apply higher qualifying NT-proBNP levels for inclusion of AF patients in clinical trials.

Editorial comment

In their editorial article, Voors and Lam [6] highlight the importance of the findings in two contexts:

  • The clinical trial context, in which higher NT-proBNP levels are required to include AF patients. The authors note that this policy may lead to a selection bias of higher risk patients, and it caps the inclusion of AF patients in these trials.
  • The clinical practice context, in which physicians thought that patients with HF and AF were ‘justified’ to have higher NT-proBNP levels, a myth that may influence the selection of therapeutic strategies.

The authors conclude: ‘Taken together, the data from the current study by Kristensen et al provide important lessons about the use of NT-proBNP in HF and AF. However, several key questions still need to be addressed, in particular the diagnostic thresholds of NPs in HF with versus without AF, the prognostic use of NPs in AF without HF, and the optimal NP cutoffs in HF with preserved ejection fraction, with and without AF.’


Show references

Find this article online at Circulation: Heart Failure

Share this page with your colleagues and friends: