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

Abstract

AIMS:

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.

METHODS AND RESULTS:

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).

CONCLUSION:

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.

• Authors: Stephen J Greene, Gregg C Fonarow, Scott D Solomon, Haris P Subacius, Andrew P Ambrosy, Muthiah Vaduganathan, Aldo P Maggioni, Michael Böhm, Eldrin F Lewis, Faiez Zannad, Javed Butler, Mihai Gheorghiade, ASTRONAUT Investigators and Coordinators
• Journal: European journal of heart failure (Eur J Heart Fail) Vol. 19 Issue 4 Pg. 552-562 (04 2017) ISSN: 1879-0844 [Electronic] England
• PMID: 27748006 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

Chemical References

• Amides
• Antihypertensive Agents
• Fumarates
• Peptide Fragments
• pro-brain natriuretic peptide (1-76)
• Natriuretic Peptide, Brain
• aliskiren

Topics

• Aged
• Amides (therapeutic use)
• Antihypertensive Agents (therapeutic use)
• Atrial Fibrillation (blood, complications)
• Atrial Flutter (blood, complications)
• Disease Progression
• Female
• Fumarates (therapeutic use)
• Heart Failure (blood, complications, drug therapy)
• Hospitalization
• Humans
• Male
• Middle Aged
• Natriuretic Peptide, Brain (blood)
• Peptide Fragments (blood)
• Prognosis
• Randomized Controlled Trials as Topic