Low‐dose digoxin improves cardiac function in patients with heart failure, preserved ejection fraction and atrial fibrillation – the RATE‐AF randomized trial

Aims To compare the effect of digoxin versus beta‐blockers on left ventricular function, in patients with permanent atrial fibrillation (AF) and symptoms of heart failure within the RATE‐AF randomized trial. Methods and results Blinded echocardiograms were performed at baseline and 12‐month follow‐up using a pre‐defined imaging protocol and the index‐beat approach. The change in systolic and diastolic function was assessed, stratified by left ventricular ejection fraction (LVEF). Overall, 145 patients completed follow‐up, with median age 75 years (interquartile range 69–82) and 44% women. In 119 patients with baseline LVEF ≥50%, a significantly greater improvement in systolic function was noted in patients randomized to low‐dose digoxin versus beta‐blockers: adjusted mean difference for LVEF 2.3% (95% confidence interval CI 0.3–4.2; p = 0.021), s′ 1.1 cm/s (95% CI 1.0–1.2; p = 0.001) and stroke volume 6.5 ml (95% CI 0.4–12.6; p = 0.037), with no difference in global longitudinal strain ( p = 0.11) or any diastolic parameters. There were no significant differences between groups for patients with LVEF 40–49% and <40%. Digoxin reduced N‐terminal pro‐B‐type natriuretic peptide compared to beta‐blockers (geometric mean difference 0.77; 95% CI 0.64–0.92; p = 0.004), improved New York Heart Association functional class (odds ratio OR 11.3, 95% CI 4.3–29.8; p < 0.001) and modified European Heart Rhythm Association arrhythmia symptom class (OR 4.91, 95% CI 2.36–10.23; p < 0.001), with substantially less adverse events (incident rate ratio 0.21, 95% CI 0.13–0.31; p < 0.001). There were no interactions between treatment effects and baseline LVEF for these outcomes (interaction p = 0.62, 0.49, 0.07 and 0.13, respectively). Conclusions Low‐dose digoxin in patients with symptoms of heart failure, preserved LVEF and permanent AF leads to a significantly greater improvement in systolic function compared to treatment with beta‐blockers.