Abstract 16993: Digoxin Use and Subsequent Clinical Outcomes in Patients With Atrial Fibrillation Without Heart Failure in the ENGAGE AF-TIMI 48 Trial
Background: Digoxin has been well studied in patients with heart failure (HF), but its role for rate control therapy in patients with atrial fibrillation (AF) without HF is controversial.
Methods: In the randomized controlled ENGAGE AF-TIMI 48 trial, clinical outcomes of patients with AF without HF at baseline were examined by baseline digoxin use using MV Cox models during a median FU of 2.8 years. HF at baseline was defined as prior or current clinical stage C or D HF. Clinical outcomes were adjudicated and included the cause of death and non-fatal events. Results were confirmed by propensity matched analysis.
Results: Out of 21,105 patients included in ENGAGE AF-TIMI 48 trial, 8981 patients (median age 75 ys, 61% male) with AF and without HF at baseline were included. Of these, 1825 patients (20%) were treated with digoxin at baseline. Permanent/ persistent AF, lower ejection fraction (EF), better renal function, and less use of beta blockers were associated with digoxin use (P<0.001 for each). Compared to patients not treated with digoxin, patients treated with digoxin had higher rates of all cause death, cardiovascular (CV) death, and sudden cardiac death (SCD), but similar rates of HF death, non-CV death, and HF hospitalizations (Figure). In MV analysis, digoxin use was significantly associated with SCD (adj HR 1.51, 95% CI 1.10-2.07), but not with the other outcomes (Figure). There was no significant interaction between digoxin use and SCD by age, sex, AF type, EF, creatinine clearance, beta blockers, or randomized treatment (P>0.05 for each). Consistent results were observed with the 3634 patients included in a propensity matched analysis (adj HR for SCD with digoxin 1.90, 95% CI 1.36-2.65).
Conclusion: In this observational study in patients with AF without HF, who are presumably treated with digoxin for rate control, digoxin use was associated with increased risk of SCD. These results highlight the need to study digoxin in patients with AF without HF in a randomized trial.
Author Disclosures: A. Eisen: Research Grant; Significant; From Daiichi Sankyo to TIMI. C.T. Ruff: Research Grant; Significant; AstraZeneca, Eisai, Intarcia. Honoraria; Significant; Boehringer Ingelheim, Daiichi Sankyo. Consultant/Advisory Board; Significant; Boehringer Ingelheim, Daiichi Sankyo. E. Braunwald: Research Grant; Modest; Astra Zeneca, Johnson & Johnson, Bristol Myers Squibb, Merck & Co., Daiichi Sankyo, Glaxo Smith Kline, Sanofi Aventis, Duke University and Novartis.. Honoraria; Modest; Merck & Co (no compensation), The Medicines Co., Medscape, Bayer, Daiichi Sankyo, Menarini International, Sanofi, Novartis (Uncompensated). R.A. Hamershock: Research Grant; Significant; From Daiichi Sankyo to TIMI. B.S. Lewis: Research Grant; Significant; Pfizer, BMS, Bayer, MSD. Consultant/Advisory Board; Significant; Pfizer, BMS, Bayer, MSD. C. Hassager: None. J. LeHeuzey: Consultant/Advisory Board; Modest; Bayer, Boehringer Ingelheim, BMS/Pfizer, Daiichi-Sankyo, Sanofi, Servier, Astra Zeneca, Meda and Correvio. M. Mercuri: Employment; Significant; Daiichi Sankyo Inc. H. Rutman: Employment; Significant; Daiichi Sankyo Inc. E.M. Antman: Research Grant; Significant; Astra Zeneca,Daiichi Sankyo,Eli Lilly and Company. R.P. Giugliano: Research Grant; Significant; Daiichi Sankyo. Honoraria; Significant; Honoraria for CME programs: Daiichi-Sankyo, American College of Cardiology. Consultant/Advisory Board; Modest; Honoraria for Consultant: Boehering Ingelheim, Bristol Myers Squibb, Merck, Portola, Pfizer. Consultant/Advisory Board; Significant; Honoraria for consultant: Daiichi Sankyo.
- © 2016 by American Heart Association, Inc.