Digoxin in patients with permanent atrial fibrillation: Data from the RACE II study

Bart A. Mulder, Dirk J. Van Veldhuisen, Harry J. G. M. Crijns, Jan G. P. Tijssen, Hans L. Hillege, Marco Alings, Michiel Rienstra, Maarten P. Van den Berg, Isabelle C. Van Gelder*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


BACKGROUND The Atrial Fibrillation Follow-up Investigation of Rhythm Management trial showed that digoxin was associated with increased mortality in patients with atrial fibrillation. OBJECTIVES To assess the association of digoxin with cardiovascular (CV) morbidity and mortality in patients with permanent atrial fibrillation enrolled in the Dutch Rate Control Efficacy in Permanent AF: A Comparison Between Lenient Versus Strict Rate Control II trial as well as to assess the role of digoxin to achieve heart rate targets. METHODS The primary outcome was a composite of CV morbidity and mortality. Secondary outcomes included CV hospitalization and all-cause mortality or heart failure (HF) hospitalization. Of the 614 patients, 608 (99%) completed the dose-adjustment phase. Outcome events were analyzed from the end of the dose-adjustment phase until the end of follow-up. The median follow-up period was 2.9 years (interquartile range 2.7-3.0 years). RESULTS In total, 284 patients (46.7%) used digoxin after the dose-adjustment phase (median dosage 0.250 mg; interquartile range 0.0625-0.750 mg). These patients were more often women, previously admitted for HF, had an increased left ventricular end-systolic diameter, and more often randomized to strict rate control. By using Cox proportional hazards regression analysis, the use of digoxin was not associated with an increased risk for the primary and secondary outcomes. For the primary outcome, the 3-year estimated cumulative incidence was 12.9% vs 13.4% in the digoxin group vs the no-digoxin group (unadjusted hazard ratio [HR] 0.97; 95% confidence interval [CI] 0.62-1.52). Incidence was 19.4% vs 19.5% for CV hospitalization (unadjusted HR 1.00; 95% CI 0.69-1.45) and 6.6% vs 9.9% for all-cause mortality or HF hospitalization (unadjusted HR 0.62; 95% CI 0.34-1.13) in the digoxin group vs the no-digoxin group. CONCLUSION The use of digoxin was not associated with increased morbidity and mortality.
Original languageEnglish
Pages (from-to)1543-1550
JournalHeart Rhythm
Issue number9
Publication statusPublished - Sept 2014


  • Atrial fibrillation
  • Digoxin
  • Morbidity
  • Mortality
  • Rate control

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