Abstract Category: 26. Clinical Electrophysiology—Supraventricular ArrhythmiasPresentation Number: 906-6Authors: Matthew G. Whitbeck, Richard Charnigo, Milagros M. Zegarra, Jignesh Shah, Gustavo X. Morales, Charles Campbell, Alison Bailey, Tracy Macaulay, Claude S. Elayi, University of Kentucky, Lexington, KY Background: Digoxin remains a widely used medication worldwide for congestive heart failure (CHF) and rate control of atrial fibrillation (AF). There are, however, conflicting data about its safety, particularly in patients with AF. Since the Digitalis Investigation Group (DIG) study, several studies have identified digoxin as a predictor of increased mortality. Our objective was to determine whether digoxin increased mortality independently of CHF and ejection fraction (EF) in patients enrolled in the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study.Methods: The AFFIRM database was analyzed using Cox proportional hazards regression modeling to determine the associations of overall and cardiovascular mortality with digoxin among patients without CHF or low EF and among patients with either CHF or low EF, controlling for cardioversions, AF type, and baseline characteristics.Results: Among patients without low EF or CHF, digoxin significantly elevated the hazard for overall mortality by an estimated 45.3% (Estimated Hazard Ratio [EHR] = 1.45, 95% CI = 1.17 to 1.8, p = 0.0006). There was also a trend toward an elevated risk of cardiovascular mortality (EHR = 1.36, 95% CI = 0.98 to 1.91, p = 0.068). Among patients with either low EF or CHF, digoxin significantly elevated the hazard for overall mortality by an estimated 41.9% (EHR = 1.42, 95% CI = 1.11 to 1.82, p = 0.0057) and for cardiovascular mortality by an estimated 49.5% (EHR = 1.49, 95% CI = 1.08 to 2.06, p = 0.0145).Conclusion: Digoxin was significantly associated with increased cardiovascular and total mortality irrespective of CHF or low EF in patients who participated in the AFFIRM study.