Influence of atrial fibrillation on post-discharge natriuretic peptide trajectory and clinical outcomes among patients hospitalized for heart failure: insights from the ASTRONAUT trial.


Journal Article

Change in NT-proBNP level is a common surrogate endpoint in early phase heart failure (HF) trials, but whether this endpoint is influenced by atrial fibrillation/flutter (AFF) is unclear.This analysis included 1358 patients from the ASTRONAUT trial, which randomized patients hospitalized for HF with EF ≤40% to aliskiren or placebo in addition to standard care. Patients were stratified by presence of AFF on baseline ECG. NT-proBNP was measured longitudinally by a core laboratory at baseline, 1 month, 6 months, and 12 months. Compared with non-AFF patients, AFF patients experienced greater reduction from baseline in log-transformed NT-proBNP (interaction P < 0.001), but this difference was not significant after adjustment (interaction P = 0.726). The ability of aliskiren to lower NT-proBNP during follow-up differed by AFF status (interaction P = 0.001), with aliskiren lowering NT-proBNP more than placebo among non-AFF patients only. After adjustment, baseline AFF was not associated with mortality or HF hospitalization at 12 months (all P ≥ 0.152).In this hospitalized HF cohort, AFF status did not influence post-discharge NT-proBNP trajectory or clinical outcomes after adjustment for patient characteristics. Aliskiren lowered follow-up NT-proBNP levels in patients without AFF, but had no influence among patients with AFF. This study generates the hypothesis that the ability of a HF trial to meet an NT-proBNP defined endpoint may be influenced by the prevalence of AFF in the population. Because aliskiren did not improve outcomes in patients without AFF, this analysis suggests changes in NT-proBNP induced by investigational therapies may be dissociated from clinical effects.

Full Text

Duke Authors

Cited Authors

  • Greene, SJ; Fonarow, GC; Solomon, SD; Subacius, HP; Ambrosy, AP; Vaduganathan, M; Maggioni, AP; Böhm, M; Lewis, EF; Zannad, F; Butler, J; Gheorghiade, M; ASTRONAUT Investigators and Coordinators,

Published Date

  • April 2017

Published In

Volume / Issue

  • 19 / 4

Start / End Page

  • 552 - 562

PubMed ID

  • 27748006

Pubmed Central ID

  • 27748006

Electronic International Standard Serial Number (EISSN)

  • 1879-0844

International Standard Serial Number (ISSN)

  • 1388-9842

Digital Object Identifier (DOI)

  • 10.1002/ejhf.674


  • eng