Rate Control Therapy Evaluation in Permanent Atrial Fibrillation - RATE-AF

Contribution To Literature:

The RATE-AF trial showed that digoxin was associated with symptom improvement and reduction in NT-proBNP compared with a beta-blocker. 


The goal of the trial was to evaluate digoxin compared with beta-blocker among patients with permanent atrial fibrillation.

Study Design

  • Randomized
  • Parallel
  • Open-label

Eligible patients were randomized to digoxin (n = 80) vs. beta-blocker (n = 80). Patients randomized to a beta-blocker received bisoprolol.

  • Total number of enrollees: 160
  • Duration of follow-up: 12 months
  • Mean patient age: 76 years
  • Percentage female: 46%

Inclusion criteria:

  • ≥60 years of age
  • Permanent atrial fibrillation
  • New York Heart Association (NYHA) ≥ class II

Exclusion criteria:

  • Heart rate <60 bpm
  • Need for beta-blocker based on heart failure or ejection fraction (EF)

Other salient features/characteristics:

  • Heart rate reduction was similar between treatment groups at 12 months

Principal Findings:

The primary outcome, patient-reported quality of life at 6 months, was similar between the groups (p = 0.30). Some quality of life measures favored digoxin at 12 months.

Secondary outcomes:

  • NYHA class: In the digoxin group, 2.4 at baseline and 1.5 at 12 months. In the beta-blocker group, 2.4 at baseline and 2.0 at 12 months (p < 0.001).
  • N-terminal pro–B-type natriuretic peptide (NT-proBNP): In the digoxin group, 1,095 at baseline and 960 at 12 months. In the beta-blocker group, 1,041 at baseline and 1,250 at 12 months (p = 0.005).
  • Left ventricular EF (LVEF): In the digoxin group, 56.2% at baseline and 59.7% at 12 months. In the beta-blocker group, 57.6% at baseline and 59.8% at 12 months (p = 0.45).
  • Adverse events: In the digoxin group, there were 29 events vs. 142 events in the beta-blocker group (p < 0.001).
  • Mean physical component summary score at 6 months was 31.5 in the digoxin group vs. 29.3 in the beta-blocker group (p = 0.3).


Among patients with permanent atrial fibrillation, digoxin compared with beta-blocker failed to improve quality of life measures at 6 months. Despite lack of benefit for digoxin on the primary outcome, digoxin improved some measures of quality of life at 12 months and was associated with greater reductions in NYHA class and NT-proBNP. Digoxin was also associated with fewer adverse events compared with beta-blockers. The overall clinical significance of these findings is unknown.


Kotecha D, Bunting KV, Gill SK, et al. Effect of Digoxin vs Bisoprolol for Heart Rate Control in Atrial Fibrillation on Patient-Reported Quality of Life: The RATE-AF Randomized Clinical Trial. JAMA 2020;324:2497-508.

Presented by Dr. Dipak Kotecha at the European Society of Cardiology Virtual Congress, August 29, 2020.

Clinical Topics: Arrhythmias and Clinical EP, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: ESC Congress, ESC20, Adrenergic beta-Antagonists, Arrhythmias, Cardiac, Atrial Fibrillation, Bisoprolol, Bradycardia, Digoxin, Geriatrics, Heart Failure, Heart Rate, Natriuretic Peptide, Brain, Quality of Life, Secondary Prevention

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