Influence of atrial fibrillation on post‐discharge natriuretic peptide trajectory and clinical outcomes among patients hospitalized for heart failure: insights from the <scp>ASTRONAUT</scp> trial

<jats:title>Abstract</jats:title><jats:sec><jats:title>Aims</jats:title><jats:p>Change in <jats:styled-content style="fixed-case">NT‐proBNP</jats:styled-content> level is a common surrogate endpoint in early phase heart failure (<jats:styled-content style="fixed-case">HF</jats:styled-content>) trials, but whether this endpoint is influenced by atrial fibrillation/flutter (<jats:styled-content style="fixed-case">AFF</jats:styled-content>) is unclear.</jats:p></jats:sec><jats:sec><jats:title>Methods and results</jats:title><jats:p>This analysis included 1358 patients from the <jats:styled-content style="fixed-case">ASTRONAUT</jats:styled-content> trial, which randomized patients hospitalized for <jats:styled-content style="fixed-case">HF</jats:styled-content> with <jats:styled-content style="fixed-case">EF</jats:styled-content> ≤40% to aliskiren or placebo in addition to standard care. Patients were stratified by presence of <jats:styled-content style="fixed-case">AFF</jats:styled-content> on baseline <jats:styled-content style="fixed-case">ECG</jats:styled-content>. <jats:styled-content style="fixed-case">NT‐proBNP</jats:styled-content> was measured longitudinally by a core laboratory at baseline, 1 month, 6 months, and 12 months. Compared with non‐<jats:styled-content style="fixed-case">AFF</jats:styled-content> patients, <jats:styled-content style="fixed-case">AFF</jats:styled-content> patients experienced greater reduction from baseline in log‐transformed <jats:styled-content style="fixed-case">NT‐proBNP</jats:styled-content> (interaction <jats:italic>P</jats:italic> < 0.001), but this difference was not significant after adjustment (interaction <jats:italic>P</jats:italic> = 0.726). The ability of aliskiren to lower <jats:styled-content style="fixed-case">NT‐proBNP</jats:styled-content> during follow‐up differed by <jats:styled-content style="fixed-case">AFF</jats:styled-content> status (interaction <jats:italic>P</jats:italic> = 0.001), with aliskiren lowering <jats:styled-content style="fixed-case">NT‐proBNP</jats:styled-content> more than placebo among non‐<jats:styled-content style="fixed-case">AFF</jats:styled-content> patients only. After adjustment, baseline <jats:styled-content style="fixed-case">AFF</jats:styled-content> was not associated with mortality or <jats:styled-content style="fixed-case">HF</jats:styled-content> hospitalization at 12 months (all <jats:italic>P</jats:italic> ≥ 0.152).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>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.</jats:p></jats:sec>